Correlation of URGCP Gene Expression in Neurotrophic Tyrosin Kinase 1,2,3 and MAPK Signal Transduction Pathways as a New Approach in Sarcomas

Correlation of URGCP Gene Expression in Neurotrophic Tyrosin Kinase 1,2,3 and MAPK Signal Transduction Pathways as a New Approach in Sarcomas | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Correlation of URGCP Gene Expression in Neurotrophic Tyrosin Kinase 1,2,3 and MAPK Signal Transduction Pathways as a New Approach in Sarcomas Zeliha Akdağ, Ferda Bir, Emel Kılıçarslan, Lale Şatıroğlu tufan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7009634/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Sarcoma is a heterogeneous malignant cancer of mesenchymal origin, and approximately 80% is soft tissue sarcoma (STS), which accounts for 1% of all malignant cancers. NTRKs, one of the gene fusions, are important factors involved in the development and differentiation of nerve cells. The MAPK signalling pathway can lead to processes such as migration, invasion and metastasis of tumour cells. URGCP is an oncogene involved in tumour development and formation in many types of cancer. Although it promotes cell proliferation through signalling pathways such as MAPK, its effect on STS and its molecular mechanism are unknown. In this study, we investigated the expression and correlations of NTRK1, 2 and 3 gene fusions, genes in the MAPK signalling pathway and URGCP oncogene in STS subtypes. First, RNA was isolated from FFPE tissues from 80 STS patients and then the expression levels of NTRK1,2,3 and MEK1,2 and ERK1 genes from the MAPK signalling pathway and URGCP oncogene were analysed by qPCR. The correlations of these genes with each other and with STS were analysed and concluded. The study revealed for the first time the association of URGCP with STS and the link between NTRK gene fusions and the MAPK signalling pathway. Soft Tissue Sarcoma Sarcoma NTRK1 2 3 MAPK Signaling Pathway URGCP Figures Figure 1 Figure 2 Figure 3 1. INTRODUCTION Sarcoma is one of the rare types of cancer of mesenchymal origin, covering 1% of all malignant cancer types occurring in connective tissue types such as bone, muscle and adipose tissue. It has more than 100 subtypes, 20% of which originate from bone and 80% from soft tissue [ 1 , 2 , 3 , 4 ]. Soft tissue sarcomas (STSs) include malignant tumours of mesenchymal origin with many histological subtypes, especially connective tissue, and are a rare type of cancer with only 1% of all malignant cancer types [ 2 , 4 ]. In our study, 12 subtypes of soft tissue sarcomas were studied. Malignant Peripheral Nerve Sheath Tumours (MPNSTs) constitute approximately 10% of all soft tissue tumours and have a high tendency to metastasise. [ 5 , 6 , 7 ]. Inflammatory Myofibroblastic Tumour; It is a very rare sarcoma of intermediate grade according to its low recurrence risk and metastatic potential [ 8 , 9 ]. Dedifferentiated Liposarcoma; It is the most heterogeneous of all sarcomas with a wide variety of histological patterns. It is a high-grade and aggressive disease and high local and metastatic recurrence rates are associated with a very high mortality [ 10 , 11 ]. Myxofibrosarcoma is one of the most common STSs. It has the highest recurrence rate among all STSs and metastasises predominantly to the lungs and bone [ 12 , 13 ]. Leiomyosarcoma is one of the most common subtypes, accounting for approximately 20% of soft tissue sarcoma cases. It has an important intrinsic aggressiveness as one of the sarcoma subtypes with the highest risk of distant recurrence and reduced disease-specific survival [ 14 , 15 ]. Synovial Sarcoma; It is the best-defined ‘translocation-associated sarcoma’ defined by the presence of a translocation involving the SS18 gene on chromosome 18 and one of several synovial sarcoma X genes on chromosome X. It is a high-grade sarcoma with an aggressive course and a high potential for early metastasis [ 16 , 17 ]. Undifferentiated Pleomorphic Sarcoma is one of the most common soft tissue sarcomas. It is a high-grade aggressive sarcoma previously called malignant fibrous histiocytoma [ 18 ]. Fibrosarcoma is a malignant neoplasm consisting of fibroblasts that may have varying amounts of collagen production and ‘herringbone’ architecture. It is a rare, highly malignant tumour of mesenchymal cell origin [ 19 ]. Fibromatosis; Fibromatosis do not metastasise; however, especially deep-seated ones show a destructive growth pattern by infiltrating the surrounding soft tissues [ 20 ]. Extrascaletal mesenchymal chondrosarcoma is a rare malignant soft tissue tumour of chondroprogenitor cell origin. It is a high-grade malignancy with a high tendency for distant metastasis [ 21 ]. Myofibroblastic; It is a rare tumour composed of malignant myofibroblasts. In addition to having a high recurrence potential, metastasis is more rare [ 22 ]. Low Grade Myxofibrosarcoma; It is one of the fibrous soft tissue sarcomas of mesenchymal origin. This rare tumour is generally seen in the extremities of elderly people [ 23 ]. Gene fusions are known to cause many different diseases. In particular, there are many chromosomal translocations associated with malignant diseases [ 24 ]. Neurotrophic tropomyosin receptor kinases (NTRKs), a gene fusion belonging to the tropomyosin receptor kinase (TRK) family, are important factors in the development and differentiation of neural cells belonging to the TRK family, as well as in maintaining neuronal homeostasis and regulating synapse formation and plasticity [ 25 , 26 ]. Mitogen-activated protein kinases (MAPKs), which have many modules, are one of the most protected signalling pathways with functions such as cell proliferation, apoptosis, tumour growth, metastasis and drug resistance [ 27 , 28 ]. Previous studies have revealed that ERK/MAPK, the most comprehensive signalling pathway, is more effective in proliferation and differentiation [ 29 , 30 ]. Cell proliferation up-regulated gene 4 (URGCP/URG4), an oncogene, was identified by Şatıroğlu-Tufan et al. as a novel gene induced by the X antigen encoded by hepatitis-B virus. URGCP is located on chromosome 7 (7p13) and promotes cell proliferation through signalling pathways such as MAPK. It is involved in tumour development and formation in many cancer types, including hepatocellular carcinoma, osteosarcoma, glioblastoma. Previous studies have shown that patients with high URGCP expression have shorter survival. Although URGCP is known to be effective in tumour formation by interacting with various signalling pathways, its effect on soft tissue sarcomas and its molecular mechanism are unknown [ 31 , 32 ]. 2. MATERIAL & METHOD 2.1 Collection of Study Samples The ethics committee approval of the study was obtained by Pamukkale University Non-Interventional Clinical Research Ethics Committee with the board decision dated 10.01.2023 and numbered 01. A total of 80 cases diagnosed as ‘Sarcoma’ diagnosed by Pamukkale University Department of Pathology and kept as archive material embedded in paraffin blocks were included in the study. A control group was not included since comparisons between subgroups would be made. Tissue samples (FFPEs) embedded in paraffin blocks fixed with 10% formaldehyde solution were used in the study. H-E and different types of immunohistochemical stained sections of all cases were re-evaluated for diagnostic and prognostic parameters. The sections that best reflected the tumour tissue and contained the areas with the least necrosis, haemorrhage, inflammatory cells and stromal elements were determined. For RNA isolation from the paraffin blocks of these sections, consecutive serial sections were taken with a 20 µm thick microtome device (Leica RM2125RT, Germany). 2.2 Total RNA Isolation, cDNA synthesis and mRNA Expression Detection by Real-Time PCR assay Qiagen mRNeasy FFPE isolation kit (Cat No: 217504) was used for total RNA isolation from paraffin embedded samples. RNA isolation was performed by deparaffinisation followed by spin columns according to the kit procedure. cDNA synthesis was performed with WIZScript™ cDNA Synthesis kit (REF:W2211) according to the procedure specified by the manufacturer. The mRNA expression changes of 7 genes including NTRK1, NTRK2, NTRK3, MEK1, MEK2, ERK1 and URGCP were determined. GAPDH was used as housekeeping for normalisation. The reverse and forward sequences of the genes are given in Table 1 . Reactions were prepared using SYBR® Green master mix and sugenomics qPCR SybrMaster kit (Catalogue No: PCR01C263) and quantitative Real-Time PCR was performed with Qiagen RotorGene device. Table 1 Forward and reverse sequences of the genes used in the study. Gene Name Gene Sequence MEK1_F 5’ GGTGTTCAAGGTCTCCCACAAG 3’ MEK1_R 5’ CACGATGTACGGCGAGTTGCAT 3’ MEK2_F 5’ GTGGTCACCAAAGTCCAGCACA 3’ MEK2_R 5’ CCACGATGTACGGAGAGTTGCA 3’ ERK1_F 5’ TGGCAAGCACTACCTGGATCAG 3’ ERK1_R 5’ GCAGAGACTGTAGGTAGTTTCGG 3’ URGCP_F 5’ CTTCATCCTGAGTCCCTACCG 3’ URGCP_R 5’ GCCGTTCTGCTGCATTCG 3’ NTRK1_F 5‘ CACTAACAGCACATCTGGAGACC 3’ NTRK1_R 5’ TGAGCACAAGGAGCAGCGTAGA 3’ NTRK2_F 5’ ACAGTCAGCTCAAGCCAGACAC 3’ NTRK2_R 5’ GTCCTGCTCAGGACAGAGGTTA 3’ NTRK3_F 5’ CCGACACTGTGGTCATTGGCAT 3’ NTRK3_R 5’ CAGTTCTCGCTTCAGCACGATG 3’ GAPDH_F 5’GTCTCCTCTGACTTCAACAGCG 3’ GAPDH_R 5’ ACCACCCTGTTGCTGTAGCCAA 3’ 2.3 Statistical Analysis The 2^(-ΔΔcT) method was used to analyse the data obtained by mRNA expression change detected by RT-PCR. The analyses were evaluated with the web-based ‘RT² Profiler™ PCR Array Data Analysis’ programme ( https://www.qiagen.com/tr/shop/genes-and-pathways/data-analysis-centeroverview-page/ ). 3. RESULTS The subtype data of the Sarcoma Patient Group were obtained from 80 paraffin embedded block samples diagnosed as different type of ‘SARCOMA’ diagnosed by Pamukkale University Department of Pathology and kept as archive material embedded in paraffin blocks. From 80 soft tissue sarcoma patients, 12 different subtypes of FFPE tissue were detected. Subtypes and patient numbers are given in Table 2 . In addition, a scatter plot is shown in Fig. 1 . Table 2 Soft tissue sarcoma subtypes and number of patients. Soft Tissue Sarcoma Subtypes Number of Patients Malignant Peripheral Nerve Sheath Tumor (MPNST) 8 Dedifferentiated Liposarcoma (DDLS) 7 Synovial Sarcoma (SS) 9 Fibrosarcoma 7 Undifferentiated Pleomorphic Sarcoma (UPS) 8 Inflammatory Myofibroblastic Tumor (IMT) 12 Myxofibrosarcoma (MFS) 8 Extrascaletal Mesenchymal Chondrosarcoma 2 Fibromatosis 1 Leiomyosarcoma (LMS) 14 Myofibrosarcoma 2 Low-Grade Myxofibrosarcoma 2 Of the 80 patient samples; malignant peripheral nerve sheath sarcoma (MPSS) 8, dedifferentiated liposarcoma (DDLS) 7, synovial sarcoma (SS) 9, fibrosarcoma 7, undifferentiated pleomorphic sarcoma (UPS) 8, inflammatory myofibroblastic sarcoma (IMT) 12, 8 in myxofibrosarcoma (MFS), 2 in extrascaletal mesenchymal chondrosarcoma, 1 in fibromatosis, 14 in leiomyosarcoma (LMS), 2 in myofibroblastic sarcoma and 2 in low grade myxofibrosarcoma. When the distribution of STS patients according to gender was analysed, 57% (n:46) of our patients were male and 43% (n:34) were female (Figure-2). Most of our patients were between the ages of 50–59 and 60–69 (Figure-2 and 3). 3.1 mRNA Expression Changes in Sarcoma Patient Group NTRK1, 2 and 3, MEK1, MEK2, ERK1 and URGCP oncogene which are downstream genes of MAPK signalling pathway and mRNA expression changes of 7 genes in total were detected by using Real-time PCR. Gene expression changes between patients were evaluated by using ct (Threshold Cycle) values determined from the patient groups as a result of PCR reactions. GAPDH was used as housekeeping for normalisation purposes. Expression changes were determined as shown in Table 3 . Fold increases for mRNA expression changes of genes and p values obtained as a result of statistical evaluation are shown in Table 3 . Table 3 Gene expression changes at mRNA level between soft tissue sarcoma subtypes and NTRK1,2,3 and MEK1,2 and ERK1, URGCP genes. Soft Tissue Sarcoma Subtypes Gene p Value Fold Change (*p < 0,05) Malignant Peripheral Nerve Sheath Tumor NTRK1 -10,94 0,281633 Malignant Peripheral Nerve Sheath Tumor NTRK2 -10,61 0,18192 Malignant Peripheral Nerve Sheath Tumor NTRK3 -6,06 0,249364 Malignant Peripheral Nerve Sheath Tumor MEK1 -6,92 0,196281 Malignant Peripheral Nerve Sheath Tumor MEK2 -3,66 0,683821 Malignant Peripheral Nerve Sheath Tumor ERK1 -2,32 0,753324 Malignant Peripheral Nerve Sheath Tumor URGCP -6,94 0,34875 Dedifferentiated Liposarcoma NTRK1 -1,42 0,333208 Dedifferentiated Liposarcoma NTRK2 1,37 0,884828 Dedifferentiated Liposarcoma NTRK3 -1,28 0,397838 Dedifferentiated Liposarcoma MEK1 -1,07 0,434377 Dedifferentiated Liposarcoma MEK2 -1,07 0,561547 Dedifferentiated Liposarcoma ERK1 3,32 0,500875 Dedifferentiated Liposarcoma URGCP -1,19 0,397512 Synovial Sarcoma NTRK1 8,85 0,823855 Synovial Sarcoma NTRK2 3,07 0,676786 Synovial Sarcoma NTRK3 7,11 0,872715 Synovial Sarcoma MEK1 6,24 0,856598 Synovial Sarcoma MEK2 7,2 0,883655 Synovial Sarcoma ERK1 25,77 0,33401 Synovial Sarcoma URGCP 5,43 0,971169 Fibrosarcoma NTRK1 10,15 0,740549 Fibrosarcoma NTRK2 1,73 0,539956 Fibrosarcoma NTRK3 7,86 0,714319 Fibrosarcoma MEK1 8,85 0,59401 Fibrosarcoma MEK2 11,62 0,523597 Fibrosarcoma ERK1 24,11 0,310417 Fibrosarcoma URGCP 9,09 0,673954 Undifferentiated Pleomorphic Sarcoma NTRK1 -3,22 0,219797 Undifferentiated Pleomorphic Sarcoma NTRK2 4,4 0,623485 Undifferentiated Pleomorphic Sarcoma NTRK3 -3,36 0,257268 Undifferentiated Pleomorphic Sarcoma MEK1 -2,27 0,984675 Undifferentiated Pleomorphic Sarcoma MEK2 -2,35 0,379809 Undifferentiated Pleomorphic Sarcoma ERK1 -3,68 0,337059 Undifferentiated Pleomorphic Sarcoma URGCP -8,04 0,243411 Inflammatory Myofibroblastic Tumor NTRK1 -9,44 0,100646 Inflammatory Myofibroblastic Tumor NTRK2 2,26 0,629345 Inflammatory Myofibroblastic Tumor NTRK3 -7,16 0,125581 Inflammatory Myofibroblastic Tumor MEK1 -13,09 0,095242 Inflammatory Myofibroblastic Tumor MEK2 -4,21 0,152371 Inflammatory Myofibroblastic Tumor ERK1 -3,49 0,450555 Inflammatory Myofibroblastic Tumor URGCP -11,95 0,10455 Myxofibrosarcoma NTRK1 -2,3 0,206836 Myxofibrosarcoma NTRK2 7,47 0,605382 Myxofibrosarcoma NTRK3 -2,33 0,224951 Myxofibrosarcoma MEK1 -3,95 0,199838 Myxofibrosarcoma MEK2 -1,19 0,276038 Myxofibrosarcoma ERK1 -1,38 0,504707 Myxofibrosarcoma URGCP -3,45 0,212101 Extrascaletal Mesenchymal Chondrosarcoma NTRK1 -4,65 NAN Extrascaletal Mesenchymal Chondrosarcoma NTRK2 3,35 NAN Extrascaletal Mesenchymal Chondrosarcoma NTRK3 -5,5 NAN Extrascaletal Mesenchymal Chondrosarcoma MEK1 -7,29 NAN Extrascaletal Mesenchymal Chondrosarcoma MEK2 -3,1 NAN Extrascaletal Mesenchymal Chondrosarcoma ERK1 -1,15 NAN Extrascaletal Mesenchymal Chondrosarcoma URGCP -5,11 NAN Fibromatosis NTRK1 -32,84 NAN Fibromatosis NTRK2 199,81 NAN Fibromatosis NTRK3 14,07 NAN Fibromatosis MEK1 16 NAN Fibromatosis MEK2 16,34 NAN Fibromatosis ERK1 8,74 NAN Fibromatosis URGCP 11,45 NAN Leiomyosarcoma NTRK1 -4,91 0,084103 Leiomyosarcoma NTRK2 3,58 0,347715 Leiomyosarcoma NTRK3 -7,13 0,131796 Leiomyosarcoma MEK1 -5,14 0,065223 Leiomyosarcoma MEK2 -2,08 0,200375 Leiomyosarcoma ERK1 -5,35 0,551473 Leiomyosarcoma URGCP -6,96 0,127702 Myofibroblastic Sarcoma NTRK1 -179,46 NAN Myofibroblastic Sarcoma NTRK2 -4,22 NAN Myofibroblastic Sarcoma NTRK3 -95,34 NAN Myofibroblastic Sarcoma MEK1 -47,18 NAN Myofibroblastic Sarcoma MEK2 -36,63 NAN Myofibroblastic Sarcoma ERK1 -61,71 NAN Myofibroblastic Sarcoma URGCP -104,51 NAN Low-Grade Myxofibrosarcoma NTRK1 -51,89 NAN Low-Grade Myxofibrosarcoma NTRK2 -3,44 NAN Low-Grade Myxofibrosarcoma NTRK3 -35,38 NAN Low-Grade Myxofibrosarcoma MEK1 -49,69 NAN Low-Grade Myxofibrosarcoma MEK2 -21,19 NAN Low-Grade Myxofibrosarcoma ERK1 -165,13 NAN Low-Grade Myxofibrosarcoma URGCP -44,55 NAN According to our results, NTRK1, 2 and 3 gene fusions were significantly increased in some soft tissue sarcoma patient groups. In synovial sarcoma NTRK1; 8,85 fold, NTRK2; 3,07 fold and NTRK3; 7,11 fold, in fibrosarcoma NTRK1; 10,15 and NTRK3; 7,86 fold, in undifferential pleomorphic sarcoma NTRK2; 4,40 fold, in inflammatory myofibroblastic sarcoma NTRK2; 2.26-fold, NTRK2; 7.47-fold in myxofibrosarcoma, NTRK2; 3.35-fold in extrascaletal mesenchymal chondrosarcoma, NTRK2; 199.81-fold, NTRK3; 14.07-fold in fibromatosis, and NTRK2; 3.58-fold in leiomyosarcoma. Statistically, the increases in mRNA levels of NTRK1, 2 and 3 genes were not found to be significant (p > 0.05). In the groups diagnosed with Extrascaletal mesenchymal chondrosarcoma, Fibromatosis, myofibroblastic and low grade myxofibrosarcoma, p value was not given because the number of patients was less than 3. In addition, in malignant peripheral nerve sheath sarcoma NTRK1; 10.94 fold, NTRK2; 10.61 fold, NTRK3; 6.06 fold, in undifferential pleomorphic sarcoma NTRK1; 3.22 fold, NTRK3; 3.36 fold, in inflammatory myofibroblastic sarcoma NTRK1; 9.44 fold, NTRK3; 7. 16 fold, NTRK1 in myxofibrosarcoma; 2.30 fold, NTRK3; 2.33 fold, NTRK1 in extra scalellar mesenchymal sarcoma; 4.65 fold, NTRK3; 5.50 fold, NTRK1 in fibromatosis; 32.84 fold, NTRK1 in leiomyosarcoma; 4.91 fold, NTRK3; 7,13 fold, in myofibroblastic sarcoma NTRK1; 179,46 fold, NTRK2; 4,22 fold, NTRK3; 95,34 fold, in low grade myxofibrosarcoma NTRK1; 51,89, NTRK2; 3,44 and NTRK3; 35,38 fold decrease were detected. These decreases were not statistically significant (p > 0.05). Since the number of patients in the groups diagnosed with Extrascaletal mesenchymal chondrosarcoma, Fibromatosis, myofibroblastic and low grade myxofibrosarcoma was less than 3, no p value was given. When we evaluated the expression of MEK1,2 and ERK1 genes involved in the MAPK signalling pathway, which are thought to be related to soft tissue sarcomas, in our patient groups, ERK1 was found to be 3.32 times higher in dedifferentiated liposarcoma and 3.32 times higher in synovial sarcoma; 3.32 fold, MEK1; 6.24, MEK2; 7.20, ERK1; 25.77 fold in synovial sarcoma, MEK1; 8.85, MEK2; 11.62, ERK1; 24.11 fold in fibrosarcoma, MEK1; 16.00, MEK2; 16.34, ERK1; 8.74 fold in fibromatosis. However, none of them were statistically significant (p > 0.05). In the mRNA expression changes of URGCP gene, which is known as a new oncogene, in soft tissue sarcoma patient groups, 5.43-fold increase in synovial sarcoma, 9.09-fold increase in fibrosarcoma and 11.45-fold increase in fibromatosis, but it was not statistically significant (p > 0.05). 4. DISCUSSION Soft tissue sarcoma is a rare cancer with a rate of 1% among all malignant cancer types. Soft tissue sarcomas seen in various age groups are more common in middle-aged patients. There are more than 100 subtypes including adult, young adult and paediatric. The incidence of soft tissue sarcomas is ranked as lower extremities, upper extremities, retroperitoneum and head and neck from most to least common [ 33 , 2 , 34 ]. With the development of molecular diagnostic technologies in the treatment of solid tumours, gene fusions as a predictive approach have increased considerably in recent years. NTRK gene family is a biomarker that may be effective in the diagnosis and treatment process in soft tissue sarcomas. The NTRK gene family consists of three genes, NTRK1, NTRK2 and NTRK3. Each encodes tropomyosin receptor kinases that interact with downstream signalling pathways. They are important parts of downstream signalling pathways involved in various effects such as cellular survival, differentiation and growth [ 25 , 35 ]. MAPK signalling pathway is a signalling cascade that plays an important role in cell proliferation, apoptosis and differentiation. Abnormal activation of the MAPK signalling pathway caused by various mechanisms such as receptor tyrosine kinases and gene mutations is involved in tumour formation and progression by contributing to many mechanisms such as cell growth, survival, invasion and metastasis [ 30 , 36 ]. Oncogenes are genes with important roles in apoptosis, proliferation and cell cycle. These genes, which play a role in cancerisation and cancer promotion, are quite numerous and more and more oncogenes are being discovered every year. One of these oncogenes is the cell proliferation up-regulated 4 gene. URGCP oncogene was first found to contribute to hepatocarcinogenesis. In later studies, it was found to be up-regulated in cancer types such as gastric cancer and osteosarcoma. For this reason, the URGCP gene is likely to be an important molecular target for cancer treatments by considering it together with its effects on the cell cycle [ 31 , 37 ] Lingxie song et al. investigated the relationship between various fusion genes and clinicopathological features of 242 cases of 7 types of soft tissue tumours by one-step RT-PCR. The study included patients from 1999 to 2021. The samples included cases of rhabdomyosarcoma (RMS), synovial sarcoma (SS), paediatric peripheral primitive neuroectodermal tumour (pPNET), alveolar soft part sarcoma (ASPS), dermatofibrosarcoma protuberans (DFSP), myxoid liposarcoma (MLPS) and soft tissue angiofibroma (AFST). By addressing the relationship between fusion gene status and clinicopathological parameters, they revealed that fusion gene status was associated with age and location but not with gender and tumour diameter [ 38 ]. In our study, similarly, we think that fusion genes could not be associated with gender and tumour diameter, but may be associated with age. Especially an increase was observed at the age of 30 years and above. NTRK fusions can be found in many different tumours and on a molecular basis, NTRK3 gene fusions are the most common, followed by NTRK1 and NTRK2 fusions. In a study by Vasiliki Siozopoulou et al. 70 FFPE fixed soft tissue and bone tumour cases were evaluated. As a result of the study, the rate of sarcoma with fusion was determined to be approximately 2.8% compared to the total population. In addition, the prognosis of NTRK1 and NTRK3-related sarcomas in relation to histomorphology was also investigated and it was found that sarcomas with NTRK1 fusion may present a low or high-grade histomorphology, and at the same time, morphologically high-grade NTRK1-containing tumours may show an aggressive course, while low-grade ones may show a more clinical course. On the other hand, sarcomas with NTRK3 fusion are more aggressive neoplasms. However, contrary to this situation, a very low grade tumour containing NTRK3 fusion was reported in the study [ 39 ]. Likewise, in our study, especially the NTRK3 fusion gene was expected to be reported in high-grade tumours, but it did not gain statistical significance. In a study conducted by Solomon et al. a total of 38,095 samples were taken from 33,997 patients and NTRK1, 2 and 3 fusion gene detection was performed. Only 13 cases out of 87 tumours and tumour types with 1915 molecular diagnoses were associated with NTRK fusions. In addition, only 3 cases of 17 inflammatory myofibroblastic tumours were associated with NTRK fusions [ 40 ]. The MAPK signalling pathway has an important role in various molecular mechanisms such as proliferation, differentiation and apoptosis in normal cells. The signalling pathway can be overactivated due to mutations, amplifications and translocations in genes responsible for the regulation of cell fate, survival and genome integrity. This can lead to cancer and tumour formation [ 41 , 42 ]. In a study conducted by Elena Arconada-Luque et al. the relationship of MAPK signalling pathway with sarcomagenesis was investigated. They compared the expression levels of different MAPKs using cell lines and mouse modelling and found no difference in ERK2 expression in tumour samples [ 43 ]. Similarly, we did not find any difference between the levels of ERK expression in our study. In addition, Yihui Gu et al. examined the relationship with the MAPK signalling pathway using MEK inhibitor in malignant peripheral nerve sheath tumours. They confirmed the overactivation of MAPK signalling pathway in malignant peripheral nerve sheath tumours [ 44 ]. In our study, no difference was observed between the expression changes of MAPK signalling pathway. The cell proliferation up-regulated 4 gene is an oncogene involved in various types of cancer. In leukaemia and prostate cancer, overexpression of URGCP gene is involved not only in tumour development but also in metastasis and recurrence [ 45 ]. The molecular mechanism of URGCP oncogene in soft tissue sarcomas is not yet known. According to the data obtained in our study, the leading reason for the statistically insignificant mRNA expression changes is the insufficient number of patients in the patient population. Since soft tissue sarcoma types are rare cancers, an equal and sufficient patient population could not be provided for each group. Therefore, no statistical significance could be drawn from the study. We think that stress, inflammation, dead receptors, oxidative stress and drugs applied in the treatment may have effects on NTRK gene fusions and MAPK signalling pathway during the consultation process of the patients in the study and therefore affect mRNA expression changes. According to the results obtained from pathology, NTRK1,2 and 3 gene fusions were reported to be negative in immunohistochemistry staining in our cases, which was similar to the findings in our study. After the URGCP oncogene, which we used in our study, was found to play a role in various types such as gastric cancer and hepatocellular cancer, it was thought that it might also have an effect on soft tissue sarcomas. However, no negative or positive effect was found in our results. For this reason, we think that it may be a pioneer for new researches with the number of patients, prognosis of the disease and diversification of examinations in future studies. Soft tissue sarcomas, which are rare among all cancer types, have more than 100 subtypes and these subtypes are malignant and rare in themselves. Therefore, the detection and prognosis of the disease have not been fully elucidated. Detection of NTRK gene fusions is a promising marker especially for the detection of STS. In our study, we examined the expression levels of NTRK gene fusions by real-time PCR. However, we think that real-time PCR should be supported by immunohistochemical staining. In addition, we anticipate that a more accurate study will be carried out with the support of new generation gene sequencing (NGS) studies, which have become widespread in recent years. We also support that by increasing the study cohort, the results will improve and may be a stepping stone for further studies. 5. CONCLUSIONS The correlation of expression levels between NTRK 1, 2 and 3 gene fusions and the MAPK signalling pathway in STS was investigated for the first time and its relationship with the URGCP oncogene was revealed for the first time. The molecular mechanism of URGCP oncogene in STS has not been determined. In our thesis study, we observed an increase in NTRK 2 gene fusions in synovial sarcoma, undifferential pleomorphic sarcoma, inflammatory myofibroblastic, myxofibrosarcoma, extrascaletal mesenchymal chondrosarcoma, fibromatosis and leiomyosarcoma, NTRK 3 gene fusions in synovial sarcoma, fibrosarcoma and fibromatosis and NTRK 1 gene fusions in synovial sarcoma and fibrosarcoma. In addition, NTRK 1 gene fusion in malignant peripheral nerve sheath sarcoma, undifferential pleomorphic sarcoma, inflammatory myofibroblastic sarcoma, myxofibrosarcoma, extrascaletal mesenchymal chondrosarcoma, fibromatosis, leiomyosarcoma, myofibroblastic sarcoma and low grade myxofibrosarcoma and malignant peripheral nerve sheath sarcoma, Decreased NTRK 3 gene fusion was observed in undifferentiated pleomorphic sarcoma, inflammatory myofibroblastic sarcoma, myxofibrosarcoma, extrascaletal mesenchymal chondrosarcoma, leiomyosarcoma, myofibroblastic sarcoma and low-grade myxofibrosarcoma sarcoma, and decreased NTRK 2 gene fusion in malignant peripheral nerve sheath sarcoma, myofibroblastic sarcoma and low-grade myxofibrosarcoma sarcoma. In dedifferentiated liposarcoma, synovial sarcoma, fibrosarcoma and fibromatosis, ERK1 of the MAPK signalling pathway and MEK1-2 were increased in synovial sarcoma, fibrosarcoma and fibromatosis. URGCP oncogene was also increased in synovial sarcoma, fibrosarcoma and fibromatosis. Despite the increases and decreases, the results were not statistically significant because the p values were greater than 0.05. In addition, p values could not be obtained because the numbers of fibromatosis, myofibroblastic sarcoma and low grade myxofibrosarcoma patients were less than 3 and 3, respectively. Our results were similar to the studies conducted in the literature and were in parallel with the pathological results. Declarations Conflict of interest The authors declare no competing financial or non-financial interests. Ethical approval The study was approved by Pamukkale University Non-Interventional Clinical Research Ethics Committee at the board meeting numbered 01 on 10.01.2023. Issue: E-60116787-020-315622 Funding This study was funded by Scientific Research Projects Coordination Unit of Pamukkale University (2023SABE001) Author contributions Yavuz Dodurga: Project administration, ınvestigation, methodology, resources, data curation, writing – review and editing, supervision, conceptualization. Zeliha Akdağ: Investigation, resources, methodology, conceptualization, writing – review and editing, data curation. Ferda Bir, Emel Kılıçarslan: methodology, validation, visualization. Lale Şatıroğlu Tufan: Validation, supervision. Acknowledgments We extend our appreciation to the Pamukkale University Scientific Research Projects Coordination Unit for their financial backing. References Bleloch JS, Ballim RD, Kimani S, Parkes J, Panieri E, Willmer T, Prince S (2017) Managing sarcoma: Where have we come from and where are we going? Therapeutic Advances in Medical Oncology, vol 9. 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The Journey of MAPK Modules in Plant Immunity. MJAVL Sciences, 11(2), 2021. https://doi.org/10.53518/mjavl959168 Braicu C, Buse M, Busuioc C, Drula R, Gulei D, Raduly L, Rusu A, Irimie A, Atanasov AG, Slaby O, Ionescu C, Berindan-Neagoe I (2019) A comprehensive review on MAPK: A promising therapeutic target in cancer. In Cancers . MDPI AG 11(10). https://doi.org/10.3390/cancers11101618 Asl ER, Amini M, Najafi S, Mansoori B, Mokhtarzadeh A, Mohammadi A, Lotfinejad P, Bagheri M, Shirjang S, Lotfi Z, Rasmi Y, Baradaran B (2021) Interplay between MAPK/ERK signaling pathway and MicroRNAs: A crucial mechanism regulating cancer cell metabolism and tumor progression. Life Sciences, vol 278. Elsevier Inc. https://doi.org/10.1016/j.lfs.2021.119499 Guo Y, Pan W, Liu S, Shen Z, Xu Y, Hu L (2020) ERK/MAPK signalling pathway and tumorigenesis (Review). Experimental and Therapeutic Medicine . https://doi.org/10.3892/etm.2020.8454 Dodurga Y, Seçme M, Lale Şatıroğlu-Tufan N (2018) A novel oncogene URG4/URGCP and its role in cancer. In Gene (Vol. 668, pp. 12–17). Elsevier B.V. https://doi.org/10.1016/j.gene.2018.05.047 Liu Y, Liu Y, Xi Y, Chen G, Wu X, He M (2020) URG4 mediates cell proliferation and cell cycle in osteosarcoma via GSK3β/β-catenin/cyclin D1 signaling pathway. J Orthop Surg Res 15(1). https://doi.org/10.1186/s13018-020-01681-y Crombé A, Kind M, Fadli D, Miceli M, Linck PA, Bianchi G, Sambri A, Spinnato P (2023) Soft-tissue sarcoma in adults: Imaging appearances, pitfalls and diagnostic algorithms. In Diagnostic and Interventional Imaging (Vol. 104, Issue 5, pp. 207–220). Elsevier Masson s.r.l. https://doi.org/10.1016/j.diii.2022.12.001 von Mehren, M., Kane, J. M., Agulnik, M., Bui, M. M., Carr-Ascher, J., Choy, E., Connelly,M., Dry, S., Ganjoo, K. N., Gonzalez, R. J., Holder, A., Homsi, J., Keedy, V., Kelly,C. M., Kim, E., Liebner, D., McCarter, M., McGarry, S. V., Mesko, N. W., … Bergman,M. A. (2022). Soft Tissue Sarcoma, Version 2.2022. JNCCN Journal of the National Comprehensive Cancer Network, 20(7), 815–833. https://doi.org/10.6004/jnccn.2022.0035 Spano M, Davis-Hayes C, Hameed M, Benayed R, Hwang S (2024) NTRK-rearranged spindle cell neoplasm: Initial observation of imaging appearance and clinicopathologic correlation. Clinical Imaging , 110 . https://doi.org/10.1016/j.clinimag.2024.110134 Smalley I, Smalley KSM (2018) ERK inhibition: A new front in the war against mapk pathway-driven cancers? Cancer Discov 8(2):140–142. https://doi.org/10.1158/2159-8290.CD-17-1355 Dodurga Y, Eroğlu C, Seçme M, Elmas L, Avcı ÇB, Şatıroğlu-Tufan NL (2016) Anti-proliferative and anti-invasive effects of ferulic acid in TT medullary thyroid cancer cells interacting with URG4/URGCP. Tumor Biology 37(2):1933–1940. https://doi.org/10.1007/s13277-015-3984-z Song L, Zhang Y, Wang Y, Xia Q, Guo D, Cao J, Xin X, Cheng H, Liu C, Jia X, Li F (2023) Detection of various fusion genes by one-step RT-PCR and the association with clinicopathological features in 242 cases of soft tissue tumor. Frontiers in Cell and Developmental Biology , 11 . https://doi.org/10.3389/fcell.2023.1214262 Siozopoulou V, Marcq E, De Winne K, Norga K, Schmitz G, Duwel V, Delvenne P, Smits E, Pauwels P (2022) NTRK Fusions in a Sarcomas Series: Pathology, Molecular and Clinical Aspects. Pathology and Oncology Research , 28 . https://doi.org/10.3389/pore.2022.1610423 Solomon JP, Linkov I, Rosado A, Mullaney K, Rosen EY, Frosina D, Jungbluth AA, Zehir A, Benayed R, Drilon A, Hyman DM, Ladanyi M, Sireci AN, Hechtman JF (2020) NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls. Mod Pathol 33(1):38–46. https://doi.org/10.1038/s41379-019-0324-7 Burotto M, Chiou VL, Lee JM, Kohn EC (2014) The MAPK pathway across different malignancies: A new perspective. In Cancer (Vol. 120, Issue 22, pp. 3446–3456). John Wiley and Sons Inc. https://doi.org/10.1002/cncr.28864 Serrano C, Romagosa C, Hernández-Losa J, Simonetti S, Valverde C, Moliné T, Somoza R, Pérez M, Vélez R, Vergés R, Domínguez R, Carles J, Ramõn Y, Cajal, S (2016) RAS/MAPK pathway hyperactivation determines poor prognosis in undifferentiated pleomorphic sarcomas. Cancer 122(1):99–107. https://doi.org/10.1002/cncr.29733 Arconada-Luque, E., Jiménez-Suarez, J., Pascual-Serra, R., Nam-Cha, S. H., Moline,T., Cimas, F. J., Fliquete, G., Ortega-Muelas, M., Roche, O., Fernández-Aroca, D.M., Muñoz Velasco, R., García-Flores, N., Garnés-García, C., Sánchez-Fdez, A., Matilla-Almazán,S., Sánchez-Arévalo Lobo, V. J., Hernández-Losa, J., Belandia, B., Pandiella, A.,… Ruiz-Hidalgo, M. J. (2022). 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J Clin Med 12(17). https://doi.org/10.3390/jcm12175477 Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 16 Jan, 2026 Reviewers invited by journal 22 Jul, 2025 Editor assigned by journal 30 Jun, 2025 First submitted to journal 30 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7009634","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":489395382,"identity":"a99bb1bf-33c2-4c28-b1c4-7d5ed80ac712","order_by":0,"name":"Zeliha Akdağ","email":"","orcid":"","institution":"Pamukkale Üniversitesi Tıp Fakültesi: Pamukkale Universitesi Tip Fakultesi","correspondingAuthor":false,"prefix":"","firstName":"Zeliha","middleName":"","lastName":"Akdağ","suffix":""},{"id":489395383,"identity":"2936a0bf-97e9-4783-90b6-abf1721f96a9","order_by":1,"name":"Ferda Bir","email":"","orcid":"","institution":"Pamukkale Üniversitesi Tıp Fakültesi: Pamukkale Universitesi Tip Fakultesi","correspondingAuthor":false,"prefix":"","firstName":"Ferda","middleName":"","lastName":"Bir","suffix":""},{"id":489395384,"identity":"a836c884-d17b-4109-8050-9824aca3d357","order_by":2,"name":"Emel Kılıçarslan","email":"","orcid":"","institution":"Pamukkale Üniversitesi Tıp Fakültesi: Pamukkale Universitesi Tip Fakultesi","correspondingAuthor":false,"prefix":"","firstName":"Emel","middleName":"","lastName":"Kılıçarslan","suffix":""},{"id":489395385,"identity":"7e9d918a-1b81-44e1-b7fb-79b6ccae2805","order_by":3,"name":"Lale Şatıroğlu tufan","email":"","orcid":"","institution":"Ankara University: Ankara Universitesi","correspondingAuthor":false,"prefix":"","firstName":"Lale","middleName":"Şatıroğlu","lastName":"tufan","suffix":""},{"id":489395386,"identity":"f241686c-b952-47db-805f-1964ea455586","order_by":4,"name":"Yavuz Dodurga","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYNACNgbGBhD9AcRmJ0UL4wwQm5kULcw8IA4hLQbHz5hJ/iizkd1w+/jFzza/tsnzMTMwfviYg0fLmRwzCYlzacYbzuUUS+f23TZsY2Zglpy5DY+WA2lpEoZthxM3nOFJkM7tuc0I1MLGzItPy/lnaRKJEC3Jvy17btsT1nIj+ZjEQbAW9mPSDD9uJxLUInnj8WHLBqBfZp7hYbPsbbid3MbM2IzXL3znExtvgkKs7wz74xs//ty2nd/efPDDRzxaFA7AmTwGDIxtIAYkJeAE8ghp9gcMDH/wKh4Fo2AUjIIRCgANWVaiskJqPQAAAABJRU5ErkJggg==","orcid":"","institution":"Pamukkale Üniversitesi Tıp Fakültesi: Pamukkale Universitesi Tip Fakultesi","correspondingAuthor":true,"prefix":"","firstName":"Yavuz","middleName":"","lastName":"Dodurga","suffix":""}],"badges":[],"createdAt":"2025-06-30 10:52:52","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7009634/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7009634/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87724548,"identity":"0841ec31-0d0c-42a0-887b-8e8ff9cf0131","added_by":"auto","created_at":"2025-07-28 10:24:28","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":172977,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution graph of soft tissue sarcoma subtypes\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7009634/v1/269f4daec0bd3b40309242f5.jpg"},{"id":87724546,"identity":"b6559a32-a0f8-4245-8a49-4b3968f34f9a","added_by":"auto","created_at":"2025-07-28 10:24:28","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":15429,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of soft tissue sarcoma cases according to gender\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7009634/v1/8d34f213215fed83768c59ab.jpg"},{"id":87724547,"identity":"5fff85fc-0beb-41b4-8e83-ffdafc696baa","added_by":"auto","created_at":"2025-07-28 10:24:28","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":85799,"visible":true,"origin":"","legend":"\u003cp\u003eAge groups and gender distribution of soft tissue sarcoma cases\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7009634/v1/c5876161de7fcf10b8b43c09.jpg"},{"id":87725893,"identity":"6e9b0107-58f9-49b6-a2f6-6324e7884432","added_by":"auto","created_at":"2025-07-28 10:40:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2685445,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7009634/v1/98f04fd9-88f0-43a8-9026-11fe6bd425f4.pdf"}],"financialInterests":"","formattedTitle":"Correlation of URGCP Gene Expression in Neurotrophic Tyrosin Kinase 1,2,3 and MAPK Signal Transduction Pathways as a New Approach in Sarcomas","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eSarcoma is one of the rare types of cancer of mesenchymal origin, covering 1% of all malignant cancer types occurring in connective tissue types such as bone, muscle and adipose tissue. It has more than 100 subtypes, 20% of which originate from bone and 80% from soft tissue [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Soft tissue sarcomas (STSs) include malignant tumours of mesenchymal origin with many histological subtypes, especially connective tissue, and are a rare type of cancer with only 1% of all malignant cancer types [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In our study, 12 subtypes of soft tissue sarcomas were studied.\u003c/p\u003e\u003cp\u003eMalignant Peripheral Nerve Sheath Tumours (MPNSTs) constitute approximately 10% of all soft tissue tumours and have a high tendency to metastasise. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Inflammatory Myofibroblastic Tumour; It is a very rare sarcoma of intermediate grade according to its low recurrence risk and metastatic potential [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Dedifferentiated Liposarcoma; It is the most heterogeneous of all sarcomas with a wide variety of histological patterns. It is a high-grade and aggressive disease and high local and metastatic recurrence rates are associated with a very high mortality [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Myxofibrosarcoma is one of the most common STSs. It has the highest recurrence rate among all STSs and metastasises predominantly to the lungs and bone [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Leiomyosarcoma is one of the most common subtypes, accounting for approximately 20% of soft tissue sarcoma cases. It has an important intrinsic aggressiveness as one of the sarcoma subtypes with the highest risk of distant recurrence and reduced disease-specific survival [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Synovial Sarcoma; It is the best-defined \u0026lsquo;translocation-associated sarcoma\u0026rsquo; defined by the presence of a translocation involving the SS18 gene on chromosome 18 and one of several synovial sarcoma X genes on chromosome X. It is a high-grade sarcoma with an aggressive course and a high potential for early metastasis [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Undifferentiated Pleomorphic Sarcoma is one of the most common soft tissue sarcomas. It is a high-grade aggressive sarcoma previously called malignant fibrous histiocytoma [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Fibrosarcoma is a malignant neoplasm consisting of fibroblasts that may have varying amounts of collagen production and \u0026lsquo;herringbone\u0026rsquo; architecture. It is a rare, highly malignant tumour of mesenchymal cell origin [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Fibromatosis; Fibromatosis do not metastasise; however, especially deep-seated ones show a destructive growth pattern by infiltrating the surrounding soft tissues [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Extrascaletal mesenchymal chondrosarcoma is a rare malignant soft tissue tumour of chondroprogenitor cell origin. It is a high-grade malignancy with a high tendency for distant metastasis [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Myofibroblastic; It is a rare tumour composed of malignant myofibroblasts. In addition to having a high recurrence potential, metastasis is more rare [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Low Grade Myxofibrosarcoma; It is one of the fibrous soft tissue sarcomas of mesenchymal origin. This rare tumour is generally seen in the extremities of elderly people [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eGene fusions are known to cause many different diseases. In particular, there are many chromosomal translocations associated with malignant diseases [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Neurotrophic tropomyosin receptor kinases (NTRKs), a gene fusion belonging to the tropomyosin receptor kinase (TRK) family, are important factors in the development and differentiation of neural cells belonging to the TRK family, as well as in maintaining neuronal homeostasis and regulating synapse formation and plasticity [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMitogen-activated protein kinases (MAPKs), which have many modules, are one of the most protected signalling pathways with functions such as cell proliferation, apoptosis, tumour growth, metastasis and drug resistance [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Previous studies have revealed that ERK/MAPK, the most comprehensive signalling pathway, is more effective in proliferation and differentiation [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCell proliferation up-regulated gene 4 (URGCP/URG4), an oncogene, was identified by Şatıroğlu-Tufan et al. as a novel gene induced by the X antigen encoded by hepatitis-B virus. URGCP is located on chromosome 7 (7p13) and promotes cell proliferation through signalling pathways such as MAPK. It is involved in tumour development and formation in many cancer types, including hepatocellular carcinoma, osteosarcoma, glioblastoma. Previous studies have shown that patients with high URGCP expression have shorter survival. Although URGCP is known to be effective in tumour formation by interacting with various signalling pathways, its effect on soft tissue sarcomas and its molecular mechanism are unknown [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e].\u003c/p\u003e"},{"header":"2. MATERIAL \u0026 METHOD","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Collection of Study Samples\u003c/h2\u003e\u003cp\u003e The ethics committee approval of the study was obtained by Pamukkale University Non-Interventional Clinical Research Ethics Committee with the board decision dated 10.01.2023 and numbered 01. A total of 80 cases diagnosed as \u0026lsquo;Sarcoma\u0026rsquo; diagnosed by Pamukkale University Department of Pathology and kept as archive material embedded in paraffin blocks were included in the study. A control group was not included since comparisons between subgroups would be made. Tissue samples (FFPEs) embedded in paraffin blocks fixed with 10% formaldehyde solution were used in the study. H-E and different types of immunohistochemical stained sections of all cases were re-evaluated for diagnostic and prognostic parameters. The sections that best reflected the tumour tissue and contained the areas with the least necrosis, haemorrhage, inflammatory cells and stromal elements were determined. For RNA isolation from the paraffin blocks of these sections, consecutive serial sections were taken with a 20 \u0026micro;m thick microtome device (Leica RM2125RT, Germany).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Total RNA Isolation, cDNA synthesis and mRNA Expression Detection by Real-Time PCR assay\u003c/h2\u003e\u003cp\u003eQiagen mRNeasy FFPE isolation kit (Cat No: 217504) was used for total RNA isolation from paraffin embedded samples. RNA isolation was performed by deparaffinisation followed by spin columns according to the kit procedure. cDNA synthesis was performed with WIZScript\u0026trade; cDNA Synthesis kit (REF:W2211) according to the procedure specified by the manufacturer. The mRNA expression changes of 7 genes including NTRK1, NTRK2, NTRK3, MEK1, MEK2, ERK1 and URGCP were determined. GAPDH was used as housekeeping for normalisation. The reverse and forward sequences of the genes are given in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Reactions were prepared using SYBR\u0026reg; Green master mix and sugenomics qPCR SybrMaster kit (Catalogue No: PCR01C263) and quantitative Real-Time PCR was performed with Qiagen RotorGene device.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eForward and reverse sequences of the genes used in the study.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGene Name\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGene Sequence\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMEK1_F\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; GGTGTTCAAGGTCTCCCACAAG 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMEK1_R\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; CACGATGTACGGCGAGTTGCAT 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMEK2_F\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; GTGGTCACCAAAGTCCAGCACA 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMEK2_R\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; CCACGATGTACGGAGAGTTGCA 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eERK1_F\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; TGGCAAGCACTACCTGGATCAG 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eERK1_R\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; GCAGAGACTGTAGGTAGTTTCGG 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eURGCP_F\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; CTTCATCCTGAGTCCCTACCG 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eURGCP_R\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; GCCGTTCTGCTGCATTCG 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNTRK1_F\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026lsquo; CACTAACAGCACATCTGGAGACC 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNTRK1_R\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; TGAGCACAAGGAGCAGCGTAGA 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNTRK2_F\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; ACAGTCAGCTCAAGCCAGACAC 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNTRK2_R\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; GTCCTGCTCAGGACAGAGGTTA 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNTRK3_F\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; CCGACACTGTGGTCATTGGCAT 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNTRK3_R\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; CAGTTCTCGCTTCAGCACGATG 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGAPDH_F\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo;GTCTCCTCTGACTTCAACAGCG 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGAPDH_R\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u0026rsquo; ACCACCCTGTTGCTGTAGCCAA 3\u0026rsquo;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Statistical Analysis\u003c/h2\u003e\u003cp\u003eThe 2^(-ΔΔcT) method was used to analyse the data obtained by mRNA expression change detected by RT-PCR. The analyses were evaluated with the web-based \u0026lsquo;RT\u0026sup2; Profiler\u0026trade; PCR Array Data Analysis\u0026rsquo; programme (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.qiagen.com/tr/shop/genes-and-pathways/data-analysis-centeroverview-page/\u003c/span\u003e\u003cspan address=\"https://www.qiagen.com/tr/shop/genes-and-pathways/data-analysis-centeroverview-page/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e"},{"header":"3. RESULTS","content":"\u003cp\u003eThe subtype data of the Sarcoma Patient Group were obtained from 80 paraffin embedded block samples diagnosed as different type of \u0026lsquo;SARCOMA\u0026rsquo; diagnosed by Pamukkale University Department of Pathology and kept as archive material embedded in paraffin blocks. From 80 soft tissue sarcoma patients, 12 different subtypes of FFPE tissue were detected. Subtypes and patient numbers are given in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. In addition, a scatter plot is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSoft tissue sarcoma subtypes and number of patients.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSoft Tissue Sarcoma Subtypes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNumber of Patients\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMalignant Peripheral Nerve Sheath Tumor (MPNST)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDedifferentiated Liposarcoma (DDLS)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSynovial Sarcoma (SS)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibrosarcoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUndifferentiated Pleomorphic Sarcoma (UPS)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInflammatory Myofibroblastic Tumor (IMT)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMyxofibrosarcoma (MFS)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eExtrascaletal Mesenchymal Chondrosarcoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibromatosis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLeiomyosarcoma (LMS)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMyofibrosarcoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLow-Grade Myxofibrosarcoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eOf the 80 patient samples; malignant peripheral nerve sheath sarcoma (MPSS) 8, dedifferentiated liposarcoma (DDLS) 7, synovial sarcoma (SS) 9, fibrosarcoma 7, undifferentiated pleomorphic sarcoma (UPS) 8, inflammatory myofibroblastic sarcoma (IMT) 12, 8 in myxofibrosarcoma (MFS), 2 in extrascaletal mesenchymal chondrosarcoma, 1 in fibromatosis, 14 in leiomyosarcoma (LMS), 2 in myofibroblastic sarcoma and 2 in low grade myxofibrosarcoma.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e When the distribution of STS patients according to gender was analysed, 57% (n:46) of our patients were male and 43% (n:34) were female (Figure-2). Most of our patients were between the ages of 50\u0026ndash;59 and 60\u0026ndash;69 (Figure-2 and 3).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e3.1 mRNA Expression Changes in Sarcoma Patient Group\u003c/h2\u003e\u003cp\u003eNTRK1, 2 and 3, MEK1, MEK2, ERK1 and URGCP oncogene which are downstream genes of MAPK signalling pathway and mRNA expression changes of 7 genes in total were detected by using Real-time PCR. Gene expression changes between patients were evaluated by using ct (Threshold Cycle) values determined from the patient groups as a result of PCR reactions. GAPDH was used as housekeeping for normalisation purposes.\u003c/p\u003e\u003cp\u003eExpression changes were determined as shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Fold increases for mRNA expression changes of genes and p values obtained as a result of statistical evaluation are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eGene expression changes at mRNA level between soft tissue sarcoma subtypes and NTRK1,2,3 and MEK1,2 and ERK1, URGCP genes.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSoft Tissue Sarcoma Subtypes\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGene\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep Value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFold Change\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e(*p\u0026thinsp;\u0026lt;\u0026thinsp;0,05)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMalignant Peripheral Nerve Sheath Tumor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNTRK1\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-10,94\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0,281633\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMalignant Peripheral Nerve Sheath Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-10,61\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,18192\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMalignant Peripheral Nerve Sheath Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-6,06\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,249364\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMalignant Peripheral Nerve Sheath Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-6,92\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,196281\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMalignant Peripheral Nerve Sheath Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-3,66\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,683821\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMalignant Peripheral Nerve Sheath Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eERK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-2,32\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,753324\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMalignant Peripheral Nerve Sheath Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eURGCP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-6,94\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,34875\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDedifferentiated Liposarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-1,42\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,333208\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDedifferentiated Liposarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e1,37\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,884828\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDedifferentiated Liposarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-1,28\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,397838\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDedifferentiated Liposarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-1,07\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,434377\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDedifferentiated Liposarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-1,07\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,561547\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDedifferentiated Liposarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eERK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e3,32\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,500875\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDedifferentiated Liposarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eURGCP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-1,19\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,397512\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSynovial Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e8,85\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,823855\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSynovial Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e3,07\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,676786\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSynovial Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e7,11\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,872715\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSynovial Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e6,24\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,856598\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSynovial Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e7,2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,883655\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSynovial Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eERK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e25,77\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,33401\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSynovial Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eURGCP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e5,43\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,971169\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e10,15\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,740549\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e1,73\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,539956\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e7,86\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,714319\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e8,85\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,59401\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e11,62\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,523597\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eERK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e24,11\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,310417\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eURGCP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e9,09\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,673954\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUndifferentiated Pleomorphic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-3,22\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,219797\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUndifferentiated Pleomorphic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e4,4\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,623485\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUndifferentiated Pleomorphic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-3,36\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,257268\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUndifferentiated Pleomorphic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-2,27\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,984675\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUndifferentiated Pleomorphic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-2,35\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,379809\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUndifferentiated Pleomorphic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eERK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-3,68\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,337059\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eUndifferentiated Pleomorphic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eURGCP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-8,04\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,243411\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInflammatory Myofibroblastic Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-9,44\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,100646\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInflammatory Myofibroblastic Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e2,26\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,629345\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInflammatory Myofibroblastic Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-7,16\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,125581\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInflammatory Myofibroblastic Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-13,09\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,095242\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInflammatory Myofibroblastic Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-4,21\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,152371\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInflammatory Myofibroblastic Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eERK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-3,49\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,450555\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInflammatory Myofibroblastic Tumor\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eURGCP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-11,95\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,10455\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-2,3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,206836\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e7,47\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,605382\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-2,33\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,224951\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-3,95\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,199838\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-1,19\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,276038\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eERK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-1,38\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,504707\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eURGCP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-3,45\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,212101\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExtrascaletal Mesenchymal Chondrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-4,65\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExtrascaletal Mesenchymal Chondrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e3,35\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExtrascaletal Mesenchymal Chondrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-5,5\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExtrascaletal Mesenchymal Chondrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-7,29\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExtrascaletal Mesenchymal Chondrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-3,1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExtrascaletal Mesenchymal Chondrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eERK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-1,15\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eExtrascaletal Mesenchymal Chondrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eURGCP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-5,11\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibromatosis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-32,84\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibromatosis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e199,81\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibromatosis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e14,07\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibromatosis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e16\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibromatosis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e16,34\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibromatosis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eERK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e8,74\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFibromatosis\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eURGCP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e11,45\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLeiomyosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-4,91\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,084103\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLeiomyosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e3,58\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,347715\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLeiomyosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-7,13\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,131796\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLeiomyosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-5,14\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,065223\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLeiomyosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-2,08\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,200375\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLeiomyosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eERK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-5,35\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,551473\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLeiomyosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eURGCP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-6,96\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0,127702\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyofibroblastic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-179,46\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyofibroblastic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-4,22\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyofibroblastic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-95,34\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyofibroblastic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-47,18\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyofibroblastic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-36,63\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyofibroblastic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eERK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-61,71\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMyofibroblastic Sarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eURGCP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-104,51\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLow-Grade Myxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-51,89\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLow-Grade Myxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-3,44\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLow-Grade Myxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eNTRK3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-35,38\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLow-Grade Myxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-49,69\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLow-Grade Myxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eMEK2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-21,19\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLow-Grade Myxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eERK1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-165,13\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLow-Grade Myxofibrosarcoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eURGCP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-44,55\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eNAN\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e According to our results, NTRK1, 2 and 3 gene fusions were significantly increased in some soft tissue sarcoma patient groups. In synovial sarcoma NTRK1; 8,85 fold, NTRK2; 3,07 fold and NTRK3; 7,11 fold, in fibrosarcoma NTRK1; 10,15 and NTRK3; 7,86 fold, in undifferential pleomorphic sarcoma NTRK2; 4,40 fold, in inflammatory myofibroblastic sarcoma NTRK2; 2.26-fold, NTRK2; 7.47-fold in myxofibrosarcoma, NTRK2; 3.35-fold in extrascaletal mesenchymal chondrosarcoma, NTRK2; 199.81-fold, NTRK3; 14.07-fold in fibromatosis, and NTRK2; 3.58-fold in leiomyosarcoma. Statistically, the increases in mRNA levels of NTRK1, 2 and 3 genes were not found to be significant (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In the groups diagnosed with Extrascaletal mesenchymal chondrosarcoma, Fibromatosis, myofibroblastic and low grade myxofibrosarcoma, p value was not given because the number of patients was less than 3. In addition, in malignant peripheral nerve sheath sarcoma NTRK1; 10.94 fold, NTRK2; 10.61 fold, NTRK3; 6.06 fold, in undifferential pleomorphic sarcoma NTRK1; 3.22 fold, NTRK3; 3.36 fold, in inflammatory myofibroblastic sarcoma NTRK1; 9.44 fold, NTRK3; 7. 16 fold, NTRK1 in myxofibrosarcoma; 2.30 fold, NTRK3; 2.33 fold, NTRK1 in extra scalellar mesenchymal sarcoma; 4.65 fold, NTRK3; 5.50 fold, NTRK1 in fibromatosis; 32.84 fold, NTRK1 in leiomyosarcoma; 4.91 fold, NTRK3; 7,13 fold, in myofibroblastic sarcoma NTRK1; 179,46 fold, NTRK2; 4,22 fold, NTRK3; 95,34 fold, in low grade myxofibrosarcoma NTRK1; 51,89, NTRK2; 3,44 and NTRK3; 35,38 fold decrease were detected. These decreases were not statistically significant (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Since the number of patients in the groups diagnosed with Extrascaletal mesenchymal chondrosarcoma, Fibromatosis, myofibroblastic and low grade myxofibrosarcoma was less than 3, no p value was given.\u003c/p\u003e\u003cp\u003eWhen we evaluated the expression of MEK1,2 and ERK1 genes involved in the MAPK signalling pathway, which are thought to be related to soft tissue sarcomas, in our patient groups, ERK1 was found to be 3.32 times higher in dedifferentiated liposarcoma and 3.32 times higher in synovial sarcoma; 3.32 fold, MEK1; 6.24, MEK2; 7.20, ERK1; 25.77 fold in synovial sarcoma, MEK1; 8.85, MEK2; 11.62, ERK1; 24.11 fold in fibrosarcoma, MEK1; 16.00, MEK2; 16.34, ERK1; 8.74 fold in fibromatosis. However, none of them were statistically significant (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eIn the mRNA expression changes of URGCP gene, which is known as a new oncogene, in soft tissue sarcoma patient groups, 5.43-fold increase in synovial sarcoma, 9.09-fold increase in fibrosarcoma and 11.45-fold increase in fibromatosis, but it was not statistically significant (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003c/div\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eSoft tissue sarcoma is a rare cancer with a rate of 1% among all malignant cancer types. Soft tissue sarcomas seen in various age groups are more common in middle-aged patients. There are more than 100 subtypes including adult, young adult and paediatric. The incidence of soft tissue sarcomas is ranked as lower extremities, upper extremities, retroperitoneum and head and neck from most to least common [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eWith the development of molecular diagnostic technologies in the treatment of solid tumours, gene fusions as a predictive approach have increased considerably in recent years. NTRK gene family is a biomarker that may be effective in the diagnosis and treatment process in soft tissue sarcomas. The NTRK gene family consists of three genes, NTRK1, NTRK2 and NTRK3. Each encodes tropomyosin receptor kinases that interact with downstream signalling pathways. They are important parts of downstream signalling pathways involved in various effects such as cellular survival, differentiation and growth [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eMAPK signalling pathway is a signalling cascade that plays an important role in cell proliferation, apoptosis and differentiation. Abnormal activation of the MAPK signalling pathway caused by various mechanisms such as receptor tyrosine kinases and gene mutations is involved in tumour formation and progression by contributing to many mechanisms such as cell growth, survival, invasion and metastasis [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOncogenes are genes with important roles in apoptosis, proliferation and cell cycle. These genes, which play a role in cancerisation and cancer promotion, are quite numerous and more and more oncogenes are being discovered every year. One of these oncogenes is the cell proliferation up-regulated 4 gene. URGCP oncogene was first found to contribute to hepatocarcinogenesis. In later studies, it was found to be up-regulated in cancer types such as gastric cancer and osteosarcoma. For this reason, the URGCP gene is likely to be an important molecular target for cancer treatments by considering it together with its effects on the cell cycle [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eLingxie song et al. investigated the relationship between various fusion genes and clinicopathological features of 242 cases of 7 types of soft tissue tumours by one-step RT-PCR. The study included patients from 1999 to 2021. The samples included cases of rhabdomyosarcoma (RMS), synovial sarcoma (SS), paediatric peripheral primitive neuroectodermal tumour (pPNET), alveolar soft part sarcoma (ASPS), dermatofibrosarcoma protuberans (DFSP), myxoid liposarcoma (MLPS) and soft tissue angiofibroma (AFST). By addressing the relationship between fusion gene status and clinicopathological parameters, they revealed that fusion gene status was associated with age and location but not with gender and tumour diameter [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. In our study, similarly, we think that fusion genes could not be associated with gender and tumour diameter, but may be associated with age. Especially an increase was observed at the age of 30 years and above.\u003c/p\u003e\u003cp\u003eNTRK fusions can be found in many different tumours and on a molecular basis, NTRK3 gene fusions are the most common, followed by NTRK1 and NTRK2 fusions. In a study by Vasiliki Siozopoulou et al. 70 FFPE fixed soft tissue and bone tumour cases were evaluated. As a result of the study, the rate of sarcoma with fusion was determined to be approximately 2.8% compared to the total population. In addition, the prognosis of NTRK1 and NTRK3-related sarcomas in relation to histomorphology was also investigated and it was found that sarcomas with NTRK1 fusion may present a low or high-grade histomorphology, and at the same time, morphologically high-grade NTRK1-containing tumours may show an aggressive course, while low-grade ones may show a more clinical course. On the other hand, sarcomas with NTRK3 fusion are more aggressive neoplasms. However, contrary to this situation, a very low grade tumour containing NTRK3 fusion was reported in the study [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Likewise, in our study, especially the NTRK3 fusion gene was expected to be reported in high-grade tumours, but it did not gain statistical significance.\u003c/p\u003e\u003cp\u003eIn a study conducted by Solomon et al. a total of 38,095 samples were taken from 33,997 patients and NTRK1, 2 and 3 fusion gene detection was performed. Only 13 cases out of 87 tumours and tumour types with 1915 molecular diagnoses were associated with NTRK fusions. In addition, only 3 cases of 17 inflammatory myofibroblastic tumours were associated with NTRK fusions [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe MAPK signalling pathway has an important role in various molecular mechanisms such as proliferation, differentiation and apoptosis in normal cells. The signalling pathway can be overactivated due to mutations, amplifications and translocations in genes responsible for the regulation of cell fate, survival and genome integrity. This can lead to cancer and tumour formation [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. In a study conducted by Elena Arconada-Luque et al. the relationship of MAPK signalling pathway with sarcomagenesis was investigated. They compared the expression levels of different MAPKs using cell lines and mouse modelling and found no difference in ERK2 expression in tumour samples [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. Similarly, we did not find any difference between the levels of ERK expression in our study. In addition, Yihui Gu et al. examined the relationship with the MAPK signalling pathway using MEK inhibitor in malignant peripheral nerve sheath tumours. They confirmed the overactivation of MAPK signalling pathway in malignant peripheral nerve sheath tumours [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. In our study, no difference was observed between the expression changes of MAPK signalling pathway.\u003c/p\u003e\u003cp\u003eThe cell proliferation up-regulated 4 gene is an oncogene involved in various types of cancer. In leukaemia and prostate cancer, overexpression of URGCP gene is involved not only in tumour development but also in metastasis and recurrence [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. The molecular mechanism of URGCP oncogene in soft tissue sarcomas is not yet known.\u003c/p\u003e\u003cp\u003eAccording to the data obtained in our study, the leading reason for the statistically insignificant mRNA expression changes is the insufficient number of patients in the patient population. Since soft tissue sarcoma types are rare cancers, an equal and sufficient patient population could not be provided for each group. Therefore, no statistical significance could be drawn from the study. We think that stress, inflammation, dead receptors, oxidative stress and drugs applied in the treatment may have effects on NTRK gene fusions and MAPK signalling pathway during the consultation process of the patients in the study and therefore affect mRNA expression changes. According to the results obtained from pathology, NTRK1,2 and 3 gene fusions were reported to be negative in immunohistochemistry staining in our cases, which was similar to the findings in our study. After the URGCP oncogene, which we used in our study, was found to play a role in various types such as gastric cancer and hepatocellular cancer, it was thought that it might also have an effect on soft tissue sarcomas. However, no negative or positive effect was found in our results. For this reason, we think that it may be a pioneer for new researches with the number of patients, prognosis of the disease and diversification of examinations in future studies.\u003c/p\u003e\u003cp\u003eSoft tissue sarcomas, which are rare among all cancer types, have more than 100 subtypes and these subtypes are malignant and rare in themselves. Therefore, the detection and prognosis of the disease have not been fully elucidated. Detection of NTRK gene fusions is a promising marker especially for the detection of STS. In our study, we examined the expression levels of NTRK gene fusions by real-time PCR. However, we think that real-time PCR should be supported by immunohistochemical staining. In addition, we anticipate that a more accurate study will be carried out with the support of new generation gene sequencing (NGS) studies, which have become widespread in recent years. We also support that by increasing the study cohort, the results will improve and may be a stepping stone for further studies.\u003c/p\u003e"},{"header":"5. CONCLUSIONS","content":"\u003cp\u003eThe correlation of expression levels between NTRK 1, 2 and 3 gene fusions and the MAPK signalling pathway in STS was investigated for the first time and its relationship with the URGCP oncogene was revealed for the first time. The molecular mechanism of URGCP oncogene in STS has not been determined.\u003c/p\u003e\u003cp\u003eIn our thesis study, we observed an increase in NTRK 2 gene fusions in synovial sarcoma, undifferential pleomorphic sarcoma, inflammatory myofibroblastic, myxofibrosarcoma, extrascaletal mesenchymal chondrosarcoma, fibromatosis and leiomyosarcoma, NTRK 3 gene fusions in synovial sarcoma, fibrosarcoma and fibromatosis and NTRK 1 gene fusions in synovial sarcoma and fibrosarcoma. In addition, NTRK 1 gene fusion in malignant peripheral nerve sheath sarcoma, undifferential pleomorphic sarcoma, inflammatory myofibroblastic sarcoma, myxofibrosarcoma, extrascaletal mesenchymal chondrosarcoma, fibromatosis, leiomyosarcoma, myofibroblastic sarcoma and low grade myxofibrosarcoma and malignant peripheral nerve sheath sarcoma, Decreased NTRK 3 gene fusion was observed in undifferentiated pleomorphic sarcoma, inflammatory myofibroblastic sarcoma, myxofibrosarcoma, extrascaletal mesenchymal chondrosarcoma, leiomyosarcoma, myofibroblastic sarcoma and low-grade myxofibrosarcoma sarcoma, and decreased NTRK 2 gene fusion in malignant peripheral nerve sheath sarcoma, myofibroblastic sarcoma and low-grade myxofibrosarcoma sarcoma.\u003c/p\u003e\u003cp\u003eIn dedifferentiated liposarcoma, synovial sarcoma, fibrosarcoma and fibromatosis, ERK1 of the MAPK signalling pathway and MEK1-2 were increased in synovial sarcoma, fibrosarcoma and fibromatosis. URGCP oncogene was also increased in synovial sarcoma, fibrosarcoma and fibromatosis. Despite the increases and decreases, the results were not statistically significant because the p values were greater than 0.05. In addition, p values could not be obtained because the numbers of fibromatosis, myofibroblastic sarcoma and low grade myxofibrosarcoma patients were less than 3 and 3, respectively. Our results were similar to the studies conducted in the literature and were in parallel with the pathological results.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eConflict of interest\u003c/h2\u003e\u003cp\u003eThe authors declare no competing financial or non-financial interests.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u003cp\u003e The study was approved by Pamukkale University Non-Interventional Clinical Research Ethics Committee at the board meeting numbered 01 on 10.01.2023. Issue: E-60116787-020-315622\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis study was funded by Scientific Research Projects Coordination Unit of Pamukkale University (2023SABE001)\u003c/p\u003e\u003ch2\u003eAuthor contributions\u003c/h2\u003e\u003cp\u003eYavuz Dodurga: Project administration, ınvestigation, methodology, resources, data curation, writing \u0026ndash; review and editing, supervision, conceptualization. Zeliha Akdağ: Investigation, resources, methodology, conceptualization, writing \u0026ndash; review and editing, data curation. Ferda Bir, Emel Kılı\u0026ccedil;arslan: methodology, validation, visualization. Lale Şatıroğlu Tufan: Validation, supervision.\u003c/p\u003e\u003ch2\u003eAcknowledgments\u003c/h2\u003e\u003cp\u003eWe extend our appreciation to the Pamukkale University Scientific Research Projects Coordination Unit for their financial backing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBleloch JS, Ballim RD, Kimani S, Parkes J, Panieri E, Willmer T, Prince S (2017) Managing sarcoma: Where have we come from and where are we going? Therapeutic Advances in Medical Oncology, vol 9. 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J Clin Med 12(17). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/jcm12175477\u003c/span\u003e\u003cspan address=\"10.3390/jcm12175477\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-applied-genetics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joag","sideBox":"Learn more about [Journal of Applied Genetics](https://www.springer.com/journal/13353)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/joag/default.aspx","title":"Journal of Applied Genetics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Soft Tissue Sarcoma, Sarcoma, NTRK1,2,3, MAPK Signaling Pathway, URGCP","lastPublishedDoi":"10.21203/rs.3.rs-7009634/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7009634/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSarcoma is a heterogeneous malignant cancer of mesenchymal origin, and approximately 80% is soft tissue sarcoma (STS), which accounts for 1% of all malignant cancers. NTRKs, one of the gene fusions, are important factors involved in the development and differentiation of nerve cells. The MAPK signalling pathway can lead to processes such as migration, invasion and metastasis of tumour cells. URGCP is an oncogene involved in tumour development and formation in many types of cancer. Although it promotes cell proliferation through signalling pathways such as MAPK, its effect on STS and its molecular mechanism are unknown. In this study, we investigated the expression and correlations of NTRK1, 2 and 3 gene fusions, genes in the MAPK signalling pathway and URGCP oncogene in STS subtypes. First, RNA was isolated from FFPE tissues from 80 STS patients and then the expression levels of NTRK1,2,3 and MEK1,2 and ERK1 genes from the MAPK signalling pathway and URGCP oncogene were analysed by qPCR. The correlations of these genes with each other and with STS were analysed and concluded. The study revealed for the first time the association of URGCP with STS and the link between NTRK gene fusions and the MAPK signalling pathway.\u003c/p\u003e","manuscriptTitle":"Correlation of URGCP Gene Expression in Neurotrophic Tyrosin Kinase 1,2,3 and MAPK Signal Transduction Pathways as a New Approach in Sarcomas","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-28 10:24:23","doi":"10.21203/rs.3.rs-7009634/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2026-01-16T13:38:42+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-22T21:50:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-30T12:34:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Applied Genetics","date":"2025-06-30T06:52:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-applied-genetics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"joag","sideBox":"Learn more about [Journal of Applied Genetics](https://www.springer.com/journal/13353)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/joag/default.aspx","title":"Journal of Applied Genetics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"fbee6a59-f713-416e-b2c4-18d3e34d6653","owner":[],"postedDate":"July 28th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-07-28T10:24:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-28 10:24:23","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7009634","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7009634","identity":"rs-7009634","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}