MiR-210 has the capacity to serve as a diagnostic biomarker for laryngeal carcinoma patient

MiR-210 has the capacity to serve as a diagnostic biomarker for laryngeal carcinoma patient | 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 Primary research MiR-210 has the capacity to serve as a diagnostic biomarker for laryngeal carcinoma patient Lili Wang, Hongguang Song, Shiming Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-105336/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Early diagnosis represents a great challenge for laryngeal carcinoma patients. MiR-210 is involved in various human cancers. In this study, we aimed to investigate the diagnostic performance of serum miR-210 in laryngeal carcinoma. Methods In our study, qRT-PCR was performed to determine the serum miR-210 level in 137 laryngeal carcinoma patients and 79 healthy volunteers. The association of serum miR-210 level with clinical characteristics of the patients was estimated by chi-square test. ROC analysis was applied to evaluate the diagnostic value of miR-210 in laryngeal carcinoma. Results Serum miR-210 level was higher in laryngeal carcinoma patients than that in healthy group ( P < 0.001). Moreover, its elevated expression was positively associated with TNM stage ( P = 0.000) and distant metastasis ( P = 0.001). The AUC value of the ROC curve was 0.893, suggesting the possibility of serum miR-210 as a diagnostic biomarker for the disease. The cut-off value was 4.685, with the sensitivity of 83.2% and the specificity of 84.8%. Conclusion MiR-210 serves as an oncogene in progression of laryngeal carcinoma. Serum miR-210 may be a potential diagnostic biomarker for laryngeal carcinoma. Cancer Biology General Cell Biology & Physiology Surgery MiR-210 Diagnosis Laryngeal carcinoma Figures Figure 1 Figure 1 Figure 2 Figure 2 Background Laryngeal carcinoma is one of the most common cancers in head and neck region, with increasing morbidity and high mortality around the world [ 1 ]. Several risk factors are confirmed for laryngeal carcinoma, such as smoking, alcohol abuse, and exposure to carcinogens, however, the etiology of the cancer still remains unclear [ 2 ]. The cancer can be curable by surgical strategies or radiotherapy at early stages, but the prognosis of patients with advanced stages are far from satisfactory [ 3 ]. Tumor stage at initial diagnosis is a pivotal factor for outcomes of patients with laryngeal carcinoma [ 4 ]. Until now, early diagnosis of laryngeal carcinoma is mainly based on conventional biopsy which is frequently performed under local or general anesthesia [ 5 ]. In addition, CT, MRI, ultrasonography, and noninvasive imaging techniques are also used for early detection of the disease, but their diagnostic accuracy can not meet the clinical requirements [ 6 – 8 ]. Thus it is urgent to identify a novel and valuable biomarker which can help to achieve the early diagnosis for the laryngeal cancer patients. MicroRNAs (miRNAs) are a class of short and non-coding RNAs with the length of 20–23 nucleotides [ 9 ]. Given their regulatory roles in gene expression at post-transcriptional level, miRNAs are involved in a variety of biological processes, including cell differentiation, proliferation, and apoptosis [ 10 ]. Dysregulation of miRNAs may contribute to occurrence and development of diseases, including cancers. MiRNAs can function as oncogenes or tumor suppressors in tumorigenesis. The expression patterns of miRNAs show significant association with tumor initiation, development and progression, suggesting their potential as predictive biomarkers for human malignancies [ 11 ]. MiRNA-210 ( MiR-210 ), a common member of miRNAs family, was reported to be involved in various human cancers, such as breast cancer, lung cancer, pancreatic carcinoma, etc [ 12 – 14 ]. However, the expression profile of serum miR-210 and its clinical significance in laryngeal carcinoma were still poorly known. In this study, we aimed to explore the expression profile of serum miR-210 in laryngeal carcinoma, as well as its association with clinicopathologic characteristics. The potential diagnostic value of miR-210 in laryngeal carcinoma was also estimated in the current study. Methods Collection of patients and specimens A total of 137 newly diagnosed laryngeal carcinoma patients were finally recruited in this study. Our study was approved by the ethics committee of Chinese PLA General Hospital. All the patients or their family signed informed consents in advance. In addition, 79 gender and age matched healthy volunteers were collected as the control group. In the control group, no one had been diagnosed with any malignancies. The blood specimens were taken from all the participants on the morning in a collection tube with EDTA. Then the samples were centrifugated at 3000 rpm for 10 min to isolate the serum sample. The supernate was stored at -80℃ until RNA extraction. The basic data of those patients with laryngeal cancer were recorded in Table 1 , including age, sex, tumor size, subsite, histologic type, TNM stage, and distant metastasis. Table 1 Association of miR-210 expression with clinicopathological characteristics of laryngeal carcinoma patients Characteristics Number N = 137 miR-210 expression P values Low (n = 59) High (n = 78) Age (years) 0.800 < 60 61 27 34 ≧ 60 76 32 44 Gender 0.257 Male 69 33 36 Female 68 26 42 Tumor size 0.374 < 3 cm 66 31 35 ≧ 3 cm 71 28 43 Subsite 0.406 Supraglottis 46 20 26 Glottis 51 25 26 Subglottis 40 14 26 Histologic type 0.301 preinvasive carcinoma 65 25 40 LSCC 72 34 38 TNM stage 0.000 I-II 71 43 28 III-IV 66 16 50 Distant metastasis 0.001 yes 69 20 49 no 68 39 29 RNA extraction and quantitative real-time polymerase chain reaction (qRT-PCR) Total RNA was extracted with the miRNeasy Mini Kit (Qiagen, Hilden Germany) following the manufacturer’s instructions. The first strand of cDNA was synthesized with the One Step PrimeScript miRNA cDNA Synthesis Kit (Takara Bio, Shiga, Japan). The relative expression level of miR-210 was measured using qRT-PCR method which was performed with a SYBR Premix Ex Taq™ kit (Takara, Dalian, China) on the Applied Biosystems 7900 Fast Real-Time PCR system (Applied Biosystems, Foster City, California, USA). U6 snRNA was used as an internal control, and the primers of miR-210 were forward: 5'-ACACTCCAGCTGGGCTGTGCGTGTGACAGCGG-3', reverse: 5’-CTCAACTGGTGTCGTGGA-3’, and primers of U6 were forward: 5'-CTCGCTTCGGCAGCACA-3', reverse: 5'-AACGCTTCACGAATTTGCGT-3'. The relative expression level of miR-210 was normalized to that of U6 and calculated using 2 −ΔΔCt method. Each test was performed in triple. Statistical analysis In this study, all statistical analyses were performed with software of SPSS 19.0 (SPSS Inc., Chicago, IL, USA) and GraphPad Prism 5 (GraphPad, San Diego, CA, USA). The serum miR-210 expression level was expressed as mean ± SD, and student’s t-tests was used to compare its differences between case and control groups. The relationship between serum miR-210 expression and various clinicopathological characteristics were assessed using Chi-square tests. To determine the diagnostic performance of serum miR-210 expression in laryngeal carcinoma, the receiver operating characteristic (ROC) curve was plotted based on the serum levels of miR-210 in healthy individuals and laryngeal cancer patients. P values < 0.05 were considered statistically significant. Results The overexpression of miR-210 in laryngeal cancer In order to investigate the expression profile of miR-210 in 137 laryngeal cancer patients and 79 healthy volunteers, the qRT-PCR was performed. As shown in Fig. 1 , the results suggested that miR-210 expression was significantly higher in laryngeal cancer tissues than that in healthy volunteers ( P < 0.001). Association between miR-210 and clinicopathological parameters of laryngeal cancer patients The patients were divided into high expression (n = 78) and low expression (n = 59) groups according to their mean expression value of miR-210 . Chi-square tests was used to evaluate the effects of miR-210 expression on clinical characteristics of laryngeal carcinoma patients. Analysis results demonstrated that miR-210 expression was significantly associated with TNM stage ( P = 0.000) and distant metastasis ( P = 0.001). However there were no obvious relationship between the expression of miR-210 and the age, gender, tumor size, subsite or histologic type of patients with laryngeal carcinoma (all P > 0.05, Table 1 ). Diagnostic value of miR-210 expression in laryngeal cancer patients In our study, ROC curve was used to determine the accuracy of miR-210 in distinguishing laryngeal cancer patients and healthy group. The AUC value of the curve was 0.893, suggesting that the laryngeal carcinoma patients could be distinguished from the healthy group based on their serum levels of miR-210 . The cut-off value of serum miR-210 for laryngeal carcinoma diagnosis was 4.685, with the sensitivity of 83.2% and the specificity of 84.8% (Fig. 2 ). Discussion Laryngeal carcinoma represents a frequently diagnosed head and neck cancer. Despite of the various available treatments, the clinical outcomes of the patients has not been significantly improved during the past three decades [ 15 ]. Low early diagnosis rate may be responsible for the high mortality [ 4 ]. Surgery and radiotherapy are effective treatments for patients diagnosed at early stages, but the therapeutic effects are limited for those diagnosed with advanced stages, due to the high recurrence rate [ 16 ]. Therefore, identification of novel biomarkers for early diagnosis may be a promising approach to improve the outcomes of the patients. As gene expression regulators, miRNAs play important roles in various biological processes, such as development, cell proliferation, apoptosis, differentiation, as well as carcinogenesis [ 17 , 18 ]. Growing evidences have demonstrated that miRNAs as oncogenes or suppressors are involved in various human malignancies. Given their functional roles in tumor progression, miRNAs are considered as promising candidate biomarkers for cancer diagnosis, prognosis, and treatments. In laryngeal cancer, a variety of miRNAs biomarkers were identified. For examples, Wu er al. reported that laryngeal cancer tissues exhibited increased expression of miR-148a and miR-375 which might serve as diagnostic biomarkers for the cancer [ 19 ]. Zhang et al. reported that up-regulation of miR-23a in laryngeal cancer showed positive correlation with aggressive clinical parameters of the patients, moreover, its elevated expression predicted poor prognosis[ 20 ]. Based on the related studies, we speculated that the expression profile of miRNAs showed significant association with tumor development and progression, and they held the potential to serve as predictive biomarkers for human malignancies. MiR-210 , a common member of miRNA family, has been determined to play an important role in tumourgenesis. The increased expression of miR-210 was observed in various cancer, such as lung adenocarcinoma, renal cell carcinoma, colorectal cancer, suggesting its carcinogenic function in these cancers [ 21 – 23 ]. In this study, we found that the expression level of miR-210 was higher in laryngeal carcinoma patients than that in healthy group. Moreover, the increased expression of miR-210 was significantly correlated with advanced TNM stage and positive distant metastasis. All the data revealed that miR-210 as a tumor oncogene played a promoting role in malignant development and progression of laryngeal carcinoma. This conclusion was consistent with the previous results obtained in other types of cancer. Given its oncogenic roles in tumorigenesis, miR-210 was identified as a biomarker for several cancers. In clear cell renal cell carcinoma, up-regulation of miR-210 showed significant association with tumor recurrence and poor prognosis of the patients, suggesting its capacity as a prognostic indicator for the disease [ 24 ]. Wang et al. reported that serum level of miR-210 was significantly higher in colorectal cancer patients than that in the healthy individuals, moreover, its elevated expression was positively correlated with malignant tumor progression and poor prognosis. Circulating miR-210 might be a potential biomarker for early detection and prognosis evaluation of the disease [ 25 ]. In this study, we estimated the diagnostic performance of serum miR-210 in laryngeal cancer. The results suggested that miR-210 could distinguish the laryngeal cancer patients from the healthy individuals with high sensitivity and specificity. MiR-210 might be a potential diagnostic biomarker for laryngeal carcinoma patients. However, the sample size was relatively small, and the application value of serum miR-210 for laryngeal carcinoma required further identification. In addition, the carcinogenic mechanisms of miR-210 in laryngeal cancer were poorly known. Further analysis were still needed to address the related issues. Conclusion In conclusion, miR-210 is elevated in laryngeal carcinoma, and positively correlated with malignant tumor progression, Serum miR-210 may be a candidate biomarker for early detection of laryngeal carcinoma. Abbreviations MicroRNAs (miRNAs) MiRNA-210 (MiR-210) quantitative real-time polymerase chain reaction (qRT-PCR) Declarations Disclosure The authors report no conflicts of interest in this work. Author Informatio Ethics approval and consent to participate This study was supported by the Ethics Committee of Chinese PLA General Hospital and also has been carried out in accordance with the World Medical Association Declaration of Helsinki. Consent for publication The subjects had been informed the objective. Certainly, written consents were signed by every subject in this study. Data availability Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. Competing interests The authors declare that they have no competing interests. Authors’ contributions L.W. design of the work; H.S. the acquisition, analysis,H.S., S.Y. interpretation of data; L.W., H.S. the creation of new software used in the work; L.W., H.S., S.Y. have drafted the work or substantively revised it. All authors read and approved the final manuscript. Acknowledgements Not applicable. 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Qu A, Du L, Yang Y, Liu H, Li J, Wang L, Liu Y, Dong Z, Zhang X, Jiang X et al : Hypoxia-inducible MiR-210 is an independent prognostic factor and contributes to metastasis in colorectal cancer . PloS one 2014, 9 (3):e90952. Samaan S, Khella HW, Girgis A, Scorilas A, Lianidou E, Gabril M, Krylov SN, Jewett M, Bjarnason GA, El-said H et al : miR-210 is a prognostic marker in clear cell renal cell carcinoma . The Journal of molecular diagnostics : JMD 2015, 17 (2):136-144. Wang W, Qu A, Liu W, Liu Y, Zheng G, Du L, Zhang X, Yang Y, Wang C, Chen X: Circulating miR-210 as a diagnostic and prognostic biomarker for colorectal cancer . European journal of cancer care 2016. Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-105336","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Primary research","associatedPublications":[],"authors":[{"id":4534484,"identity":"c0c1672a-03db-4dbf-ae9a-28648fab6082","order_by":0,"name":"Lili Wang","email":"","orcid":"","institution":"Chinese PLA General Hospital","correspondingAuthor":false,"prefix":"","firstName":"Lili","middleName":"","lastName":"Wang","suffix":""},{"id":4534485,"identity":"ee59e08e-de2f-43d1-adf4-21325e9eeba6","order_by":1,"name":"Hongguang Song","email":"","orcid":"","institution":"Beijing DCN Orthopaedic Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hongguang","middleName":"","lastName":"Song","suffix":""},{"id":4534486,"identity":"80eee8e9-6a1a-4316-a8ac-c9052851dba5","order_by":2,"name":"Shiming Yang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAsklEQVRIiWNgGAWjYDACCQaGD0BSjo29/QDRWhhnAEljPp4zCSRpYUicJ+FgQJwO+dm9Bxs+7rBIb5NgSGD4UbGNsBaDO+cSG2eekchtk248wNhz5jYRWiRyzB/ztgG1yBxIYGZsI0KL/Iwcw2aglnQ2iQQD4rQw3IBoSSBei8GdM4aNM9skDNuAgXyQKL/Iz+4xbPjYVicv395+8MGPCmIchgwOkKh+FIyCUTAKRgEuAABXETpkag+RgAAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0002-4203-4837","institution":"Chinese PLA General Hospital","correspondingAuthor":true,"prefix":"","firstName":"Shiming","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2020-11-09 19:26:48","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-105336/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-105336/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":3639471,"identity":"a807e658-9810-4b9b-a693-4923916cef56","added_by":"auto","created_at":"2020-11-17 18:28:36","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":136343,"visible":true,"origin":"","legend":"The relative expression of serum miR-210 in laryngeal cancer cases and healthy individuals. The expression of serum miR-210 was significantly increased in laryngeal cancer patients, compared to the healthy controls. ***: suggested P\u003c0.001.","description":"","filename":"Onlinefloatimage1.Png","url":"https://assets-eu.researchsquare.com/files/rs-105336/v1/e8d288d2dc9448b54b0280ec.Png"},{"id":3639467,"identity":"be43d33a-da83-48c9-be27-519f620172e2","added_by":"auto","created_at":"2020-11-17 18:28:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":136343,"visible":true,"origin":"","legend":"The relative expression of serum miR-210 in laryngeal cancer cases and healthy individuals. The expression of serum miR-210 was significantly increased in laryngeal cancer patients, compared to the healthy controls. ***: suggested P\u003c0.001.","description":"","filename":"Onlinefloatimage1.Png","url":"https://assets-eu.researchsquare.com/files/rs-105336/v1/d511866d412c0cf0371307e4.Png"},{"id":3639472,"identity":"cdf63be9-9d52-450b-9de1-a60ba41e1a71","added_by":"auto","created_at":"2020-11-17 18:28:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":95707,"visible":true,"origin":"","legend":"ROC analysis for evaluation of the diagnostic accuracy of serum miR-210 in laryngeal cancer. The curve demonstrated that serum miR-210 could discriminate between laryngeal cancer patients and healthy individuals at the cut-off value of 4.638, with the AUC value of 0.893, combining with the sensitivity of 83.2% and the specificity of 84.8%.","description":"","filename":"Onlinefloatimage2.Png","url":"https://assets-eu.researchsquare.com/files/rs-105336/v1/983536575db9d5bc9bef3691.Png"},{"id":3639468,"identity":"39049b42-9179-481f-a7c2-9a31fa25e447","added_by":"auto","created_at":"2020-11-17 18:28:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":95707,"visible":true,"origin":"","legend":"ROC analysis for evaluation of the diagnostic accuracy of serum miR-210 in laryngeal cancer. The curve demonstrated that serum miR-210 could discriminate between laryngeal cancer patients and healthy individuals at the cut-off value of 4.638, with the AUC value of 0.893, combining with the sensitivity of 83.2% and the specificity of 84.8%.","description":"","filename":"Onlinefloatimage2.Png","url":"https://assets-eu.researchsquare.com/files/rs-105336/v1/1a2b0830e4b91c0e8f789463.Png"},{"id":15671129,"identity":"01d6adef-176e-47be-b12b-72f88eeee902","added_by":"auto","created_at":"2021-11-18 14:04:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1407004,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-105336/v1/8e3fe5d6-5b7f-4f0f-99f4-ebf5206026f9.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003e\u003cem\u003eMiR-210\u003c/em\u003e has the capacity to serve as a diagnostic biomarker for laryngeal carcinoma patient\u003c/p\u003e","fulltext":[{"header":"Background","content":" \u003cp\u003eLaryngeal carcinoma is one of the most common cancers in head and neck region, with increasing morbidity and high mortality around the world [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Several risk factors are confirmed for laryngeal carcinoma, such as smoking, alcohol abuse, and exposure to carcinogens, however, the etiology of the cancer still remains unclear [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The cancer can be curable by surgical strategies or radiotherapy at early stages, but the prognosis of patients with advanced stages are far from satisfactory [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Tumor stage at initial diagnosis is a pivotal factor for outcomes of patients with laryngeal carcinoma [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Until now, early diagnosis of laryngeal carcinoma is mainly based on conventional biopsy which is frequently performed under local or general anesthesia [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In addition, CT, MRI, ultrasonography, and noninvasive imaging techniques are also used for early detection of the disease, but their diagnostic accuracy can not meet the clinical requirements [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Thus it is urgent to identify a novel and valuable biomarker which can help to achieve the early diagnosis for the laryngeal cancer patients.\u003c/p\u003e \u003cp\u003eMicroRNAs (miRNAs) are a class of short and non-coding RNAs with the length of 20\u0026ndash;23 nucleotides [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Given their regulatory roles in gene expression at post-transcriptional level, miRNAs are involved in a variety of biological processes, including cell differentiation, proliferation, and apoptosis [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Dysregulation of miRNAs may contribute to occurrence and development of diseases, including cancers. MiRNAs can function as oncogenes or tumor suppressors in tumorigenesis. The expression patterns of miRNAs show significant association with tumor initiation, development and progression, suggesting their potential as predictive biomarkers for human malignancies [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. MiRNA-210 (\u003cem\u003eMiR-210\u003c/em\u003e), a common member of miRNAs family, was reported to be involved in various human cancers, such as breast cancer, lung cancer, pancreatic carcinoma, etc [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, the expression profile of serum \u003cem\u003emiR-210\u003c/em\u003e and its clinical significance in laryngeal carcinoma were still poorly known.\u003c/p\u003e \u003cp\u003eIn this study, we aimed to explore the expression profile of serum \u003cem\u003emiR-210\u003c/em\u003e in laryngeal carcinoma, as well as its association with clinicopathologic characteristics. The potential diagnostic value of \u003cem\u003emiR-210\u003c/em\u003e in laryngeal carcinoma was also estimated in the current study.\u003c/p\u003e "},{"header":"Methods","content":" \u003cp\u003eCollection of patients and specimens\u003c/p\u003e \u003cp\u003eA total of 137 newly diagnosed laryngeal carcinoma patients were finally recruited in this study. Our study was approved by the ethics committee of Chinese PLA General Hospital. All the patients or their family signed informed consents in advance. In addition, 79 gender and age matched healthy volunteers were collected as the control group. In the control group, no one had been diagnosed with any malignancies. The blood specimens were taken from all the participants on the morning in a collection tube with EDTA. Then the samples were centrifugated at 3000\u0026nbsp;rpm for 10\u0026nbsp;min to isolate the serum sample. The supernate was stored at -80℃ until RNA extraction. The basic data of those patients with laryngeal cancer were recorded in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, including age, sex, tumor size, subsite, histologic type, TNM stage, and distant metastasis.\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\u003eAssociation of \u003cem\u003emiR-210\u003c/em\u003e expression with clinicopathological characteristics of laryngeal carcinoma patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNumber\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;137\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003e\u003cem\u003emiR-210\u003c/em\u003e expression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e values\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow (n\u0026thinsp;=\u0026thinsp;59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHigh (n\u0026thinsp;=\u0026thinsp;78)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.800\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e≧\u0026thinsp;60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.257\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eTumor size\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.374\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;3\u0026nbsp;cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e≧\u0026thinsp;3\u0026nbsp;cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eSubsite\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.406\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSupraglottis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGlottis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubglottis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eHistologic type\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.301\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003epreinvasive carcinoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLSCC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eTNM stage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI-II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII-IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eDistant metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29\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\u003eRNA extraction and quantitative real-time polymerase chain reaction (qRT-PCR)\u003c/p\u003e \u003cp\u003eTotal RNA was extracted with the miRNeasy Mini Kit (Qiagen, Hilden Germany) following the manufacturer\u0026rsquo;s instructions. The first strand of cDNA was synthesized with the One Step PrimeScript miRNA cDNA Synthesis Kit (Takara Bio, Shiga, Japan). The relative expression level of \u003cem\u003emiR-210\u003c/em\u003e was measured using qRT-PCR method which was performed with a SYBR Premix Ex Taq\u0026trade; kit (Takara, Dalian, China) on the Applied Biosystems 7900 Fast Real-Time PCR system (Applied Biosystems, Foster City, California, USA). \u003cem\u003eU6\u003c/em\u003e snRNA was used as an internal control, and the primers of \u003cem\u003emiR-210\u003c/em\u003e were forward: 5'-ACACTCCAGCTGGGCTGTGCGTGTGACAGCGG-3', reverse: 5\u0026rsquo;-CTCAACTGGTGTCGTGGA-3\u0026rsquo;, and primers of \u003cem\u003eU6\u003c/em\u003e were forward: 5'-CTCGCTTCGGCAGCACA-3', reverse: 5'-AACGCTTCACGAATTTGCGT-3'. The relative expression level of \u003cem\u003emiR-210\u003c/em\u003e was normalized to that of \u003cem\u003eU6\u003c/em\u003e and calculated using 2\u003csup\u003e\u0026minus;ΔΔCt\u003c/sup\u003e method. Each test was performed in triple.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eIn this study, all statistical analyses were performed with software of SPSS 19.0 (SPSS Inc., Chicago, IL, USA) and GraphPad Prism 5 (GraphPad, San Diego, CA, USA). The serum \u003cem\u003emiR-210\u003c/em\u003e expression level was expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, and student\u0026rsquo;s t-tests was used to compare its differences between case and control groups. The relationship between serum \u003cem\u003emiR-210\u003c/em\u003e expression and various clinicopathological characteristics were assessed using Chi-square tests. To determine the diagnostic performance of serum \u003cem\u003emiR-210\u003c/em\u003e expression in laryngeal carcinoma, the receiver operating characteristic (ROC) curve was plotted based on the serum levels of \u003cem\u003emiR-210\u003c/em\u003e in healthy individuals and laryngeal cancer patients. \u003cem\u003eP\u003c/em\u003e values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e "},{"header":"Results","content":" \u003cp\u003eThe overexpression of \u003cem\u003emiR-210\u003c/em\u003e in laryngeal cancer\u003c/p\u003e \u003cp\u003eIn order to investigate the expression profile of \u003cem\u003emiR-210\u003c/em\u003e in 137 laryngeal cancer patients and 79 healthy volunteers, the qRT-PCR was performed. As shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, the results suggested that \u003cem\u003emiR-210\u003c/em\u003e expression was significantly higher in laryngeal cancer tissues than that in healthy volunteers (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAssociation between \u003cem\u003emiR-210\u003c/em\u003e and clinicopathological parameters of laryngeal cancer patients\u003c/p\u003e \u003cp\u003eThe patients were divided into high expression (n\u0026thinsp;=\u0026thinsp;78) and low expression (n\u0026thinsp;=\u0026thinsp;59) groups according to their mean expression value of \u003cem\u003emiR-210\u003c/em\u003e. Chi-square tests was used to evaluate the effects of \u003cem\u003emiR-210\u003c/em\u003e expression on clinical characteristics of laryngeal carcinoma patients. Analysis results demonstrated that \u003cem\u003emiR-210\u003c/em\u003e expression was significantly associated with TNM stage (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.000) and distant metastasis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). However there were no obvious relationship between the expression of \u003cem\u003emiR-210\u003c/em\u003e and the age, gender, tumor size, subsite or histologic type of patients with laryngeal carcinoma (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05, Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDiagnostic value of \u003cem\u003emiR-210\u003c/em\u003e expression in laryngeal cancer patients\u003c/p\u003e \u003cp\u003eIn our study, ROC curve was used to determine the accuracy of \u003cem\u003emiR-210\u003c/em\u003e in distinguishing laryngeal cancer patients and healthy group. The AUC value of the curve was 0.893, suggesting that the laryngeal carcinoma patients could be distinguished from the healthy group based on their serum levels of \u003cem\u003emiR-210\u003c/em\u003e. The cut-off value of serum \u003cem\u003emiR-210\u003c/em\u003e for laryngeal carcinoma diagnosis was 4.685, with the sensitivity of 83.2% and the specificity of 84.8% (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eLaryngeal carcinoma represents a frequently diagnosed head and neck cancer. Despite of the various available treatments, the clinical outcomes of the patients has not been significantly improved during the past three decades [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Low early diagnosis rate may be responsible for the high mortality [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Surgery and radiotherapy are effective treatments for patients diagnosed at early stages, but the therapeutic effects are limited for those diagnosed with advanced stages, due to the high recurrence rate [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Therefore, identification of novel biomarkers for early diagnosis may be a promising approach to improve the outcomes of the patients.\u003c/p\u003e \u003cp\u003eAs gene expression regulators, miRNAs play important roles in various biological processes, such as development, cell proliferation, apoptosis, differentiation, as well as carcinogenesis [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Growing evidences have demonstrated that miRNAs as oncogenes or suppressors are involved in various human malignancies. Given their functional roles in tumor progression, miRNAs are considered as promising candidate biomarkers for cancer diagnosis, prognosis, and treatments. In laryngeal cancer, a variety of miRNAs biomarkers were identified. For examples, Wu er al. reported that laryngeal cancer tissues exhibited increased expression of \u003cem\u003emiR-148a\u003c/em\u003e and \u003cem\u003emiR-375\u003c/em\u003e which might serve as diagnostic biomarkers for the cancer [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Zhang et al. reported that up-regulation of \u003cem\u003emiR-23a\u003c/em\u003e in laryngeal cancer showed positive correlation with aggressive clinical parameters of the patients, moreover, its elevated expression predicted poor prognosis[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Based on the related studies, we speculated that the expression profile of miRNAs showed significant association with tumor development and progression, and they held the potential to serve as predictive biomarkers for human malignancies.\u003c/p\u003e \u003cp\u003e \u003cem\u003eMiR-210\u003c/em\u003e, a common member of miRNA family, has been determined to play an important role in tumourgenesis. The increased expression of \u003cem\u003emiR-210\u003c/em\u003e was observed in various cancer, such as lung adenocarcinoma, renal cell carcinoma, colorectal cancer, suggesting its carcinogenic function in these cancers [\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In this study, we found that the expression level of \u003cem\u003emiR-210\u003c/em\u003e was higher in laryngeal carcinoma patients than that in healthy group. Moreover, the increased expression of \u003cem\u003emiR-210\u003c/em\u003e was significantly correlated with advanced TNM stage and positive distant metastasis. All the data revealed that \u003cem\u003emiR-210\u003c/em\u003e as a tumor oncogene played a promoting role in malignant development and progression of laryngeal carcinoma. This conclusion was consistent with the previous results obtained in other types of cancer.\u003c/p\u003e \u003cp\u003eGiven its oncogenic roles in tumorigenesis, \u003cem\u003emiR-210\u003c/em\u003e was identified as a biomarker for several cancers. In clear cell renal cell carcinoma, up-regulation of \u003cem\u003emiR-210\u003c/em\u003e showed significant association with tumor recurrence and poor prognosis of the patients, suggesting its capacity as a prognostic indicator for the disease [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Wang et al. reported that serum level of \u003cem\u003emiR-210\u003c/em\u003e was significantly higher in colorectal cancer patients than that in the healthy individuals, moreover, its elevated expression was positively correlated with malignant tumor progression and poor prognosis. Circulating \u003cem\u003emiR-210\u003c/em\u003e might be a potential biomarker for early detection and prognosis evaluation of the disease [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In this study, we estimated the diagnostic performance of serum \u003cem\u003emiR-210\u003c/em\u003e in laryngeal cancer. The results suggested that \u003cem\u003emiR-210\u003c/em\u003e could distinguish the laryngeal cancer patients from the healthy individuals with high sensitivity and specificity. \u003cem\u003eMiR-210\u003c/em\u003e might be a potential diagnostic biomarker for laryngeal carcinoma patients. However, the sample size was relatively small, and the application value of serum \u003cem\u003emiR-210\u003c/em\u003e for laryngeal carcinoma required further identification. In addition, the carcinogenic mechanisms of \u003cem\u003emiR-210\u003c/em\u003e in laryngeal cancer were poorly known. Further analysis were still needed to address the related issues.\u003c/p\u003e "},{"header":"Conclusion","content":" \u003cp\u003eIn conclusion, \u003cem\u003emiR-210\u003c/em\u003e is elevated in laryngeal carcinoma, and positively correlated with malignant tumor progression, Serum \u003cem\u003emiR-210\u003c/em\u003e may be a candidate biomarker for early detection of laryngeal carcinoma.\u003c/p\u003e "},{"header":"Abbreviations","content":" \u003cp\u003eMicroRNAs (miRNAs)\u003c/p\u003e \u003cp\u003eMiRNA-210 (MiR-210)\u003c/p\u003e \u003cp\u003equantitative real-time polymerase chain reaction (qRT-PCR)\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDisclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report no conflicts of interest in this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Informatio\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Ethics Committee of Chinese PLA General Hospital and also has been carried out in accordance with the World Medical Association Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe subjects had been informed the objective. Certainly, written consents were signed by every subject in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData sharing is not applicable to this article as no datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eL.W. design of the work; H.S. the acquisition, analysis,H.S., S.Y. interpretation of data; L.W., H.S. the creation of new software used in the work; L.W., H.S., S.Y. have drafted the work or substantively revised it. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLi L, Wang J, Gao L, Gong L: \u003cstrong\u003eExpression of paxillin in laryngeal squamous cell carcinoma and its prognostic value\u003c/strong\u003e. \u003cem\u003eInternational journal of clinical and experimental pathology \u003c/em\u003e2015, \u003cstrong\u003e8\u003c/strong\u003e(8):9232-9239.\u003c/li\u003e\n\u003cli\u003eMarkou K, Christoforidou A, Karasmanis I, Tsiropoulos G, Triaridis S, Constantinidis I, Vital V, Nikolaou A: \u003cstrong\u003eLaryngeal cancer: epidemiological data from Nuorthern Greece and review of the literature\u003c/strong\u003e. \u003cem\u003eHippokratia \u003c/em\u003e2013, \u003cstrong\u003e17\u003c/strong\u003e(4):313-318.\u003c/li\u003e\n\u003cli\u003eZou Y, Fang F, Ding YJ, Dai MY, Yi X, Chen C, Tao ZZ, Chen SM: \u003cstrong\u003eNotch 2 signaling contributes to cell growth, anti-apoptosis and metastasis in laryngeal squamous cell carcinoma\u003c/strong\u003e. \u003cem\u003eMolecular medicine reports \u003c/em\u003e2016, \u003cstrong\u003e14\u003c/strong\u003e(4):3517-3524.\u003c/li\u003e\n\u003cli\u003eFleskens SA, Bergshoeff VE, Voogd AC, van Velthuysen ML, Bot FJ, Speel EJ, Kremer B, Takes R, Slootweg P: \u003cstrong\u003eInterobserver variability of laryngeal mucosal premalignant lesions: a histopathological evaluation\u003c/strong\u003e. \u003cem\u003eModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc \u003c/em\u003e2011, \u003cstrong\u003e24\u003c/strong\u003e(7):892-898.\u003c/li\u003e\n\u003cli\u003eLi P, Liu H, Wang Z, He F, Wang H, Shi Z, Yang A, Ye J: \u003cstrong\u003eMicroRNAs in laryngeal cancer: implications for diagnosis, prognosis and therapy\u003c/strong\u003e. \u003cem\u003eAmerican journal of translational research \u003c/em\u003e2016, \u003cstrong\u003e8\u003c/strong\u003e(5):1935-1944.\u003c/li\u003e\n\u003cli\u003eBecker M, Zaidi H: \u003cstrong\u003eImaging in head and neck squamous cell carcinoma: the potential role of PET/MRI\u003c/strong\u003e. \u003cem\u003eThe British journal of radiology \u003c/em\u003e2014, \u003cstrong\u003e87\u003c/strong\u003e(1036):20130677.\u003c/li\u003e\n\u003cli\u003eGuenzel T, Franzen A, Wiegand S, Kraetschmer S, Jahn JL, Mironczuk R, Wilhelm T, Schrom T: \u003cstrong\u003eThe value of PET compared to MRI in malignant head and neck tumors\u003c/strong\u003e. \u003cem\u003eAnticancer research \u003c/em\u003e2013, \u003cstrong\u003e33\u003c/strong\u003e(3):1141-1146.\u003c/li\u003e\n\u003cli\u003eJohnson JT, Branstetter BFt: \u003cstrong\u003ePET/CT in head and neck oncology: State-of-the-art 2013\u003c/strong\u003e. \u003cem\u003eThe Laryngoscope \u003c/em\u003e2014, \u003cstrong\u003e124\u003c/strong\u003e(4):913-915.\u003c/li\u003e\n\u003cli\u003eBartel DP: \u003cstrong\u003eMicroRNAs: target recognition and regulatory functions\u003c/strong\u003e. \u003cem\u003eCell \u003c/em\u003e2009, \u003cstrong\u003e136\u003c/strong\u003e(2):215-233.\u003c/li\u003e\n\u003cli\u003eBarba M, Felsani A, Rinaldi M, Giunta S, Malorni W, Paggi MG: \u003cstrong\u003eReducing the risk of overdiagnosis in lung cancer: a support from molecular biology\u003c/strong\u003e. \u003cem\u003eJournal of cellular physiology \u003c/em\u003e2011, \u003cstrong\u003e226\u003c/strong\u003e(9):2213-2214.\u003c/li\u003e\n\u003cli\u003eIorio MV, Croce CM: \u003cstrong\u003eMicroRNA dysregulation in cancer: diagnostics, monitoring and therapeutics. 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In this study, we aimed to investigate the diagnostic performance of serum \u003cem\u003emiR-210\u003c/em\u003e in laryngeal carcinoma.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn our study, qRT-PCR was performed to determine the serum \u003cem\u003emiR-210\u003c/em\u003e level in 137 laryngeal carcinoma patients and 79 healthy volunteers. The association of serum \u003cem\u003emiR-210\u003c/em\u003e level with clinical characteristics of the patients was estimated by chi-square test. ROC analysis was applied to evaluate the diagnostic value of \u003cem\u003emiR-210\u003c/em\u003e in laryngeal carcinoma.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSerum \u003cem\u003emiR-210\u003c/em\u003e level was higher in laryngeal carcinoma patients than that in healthy group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Moreover, its elevated expression was positively associated with TNM stage (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.000) and distant metastasis (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). The AUC value of the ROC curve was 0.893, suggesting the possibility of serum miR-210 as a diagnostic biomarker for the disease. The cut-off value was 4.685, with the sensitivity of 83.2% and the specificity of 84.8%.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003e \u003cem\u003eMiR-210\u003c/em\u003e serves as an oncogene in progression of laryngeal carcinoma. Serum \u003cem\u003emiR-210\u003c/em\u003e may be a potential diagnostic biomarker for laryngeal carcinoma.\u003c/p\u003e","manuscriptTitle":"MiR-210 has the capacity to serve as a diagnostic biomarker for laryngeal carcinoma patient","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-11-17 18:28:28","doi":"10.21203/rs.3.rs-105336/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"26a134c4-764b-45c6-936f-d3b3587a2654","owner":[],"postedDate":"November 17th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":1099287,"name":"Cancer Biology"},{"id":1099288,"name":"General Cell Biology \u0026 Physiology"},{"id":1099289,"name":"Surgery"}],"tags":[],"updatedAt":"2020-11-17T18:28:30+00:00","versionOfRecord":[],"versionCreatedAt":"2020-11-17 18:28:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-105336","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-105336","identity":"rs-105336","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}