Study on the small breast epithelial mucin tumor tissue expression difference and its relationship with survival in triple-negative breast cancer patients in Han, Miao and Buyi ethnic

Study on the small breast epithelial mucin tumor tissue expression difference and its relationship with survival in triple-negative breast cancer patients in Han, Miao and Buyi ethnic | 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 Study on the small breast epithelial mucin tumor tissue expression difference and its relationship with survival in triple-negative breast cancer patients in Han, Miao and Buyi ethnic Liu Liang, Ye Weilin, Liu Hui, Lu Qili, Wang Jun, Yang Yan, He Yang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-56422/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 Objective: To investigate Small breast epithelial mucin(SBEM) expression difference in mammary tissues and relationship with survival in thetriple-negative breast cancer(TNBC) patients in Han, Buyi and Miao ethnic. Methods : In our study, SBEM protein expressions were detected by means of immunohistochemistry in 297 patients diagnosed from 2014 to 2015,including 99 normal breast tissue specimens, 99 cases of breast benign tumor tissue specimens and 99 tissues specimens from TNBC patients.Each set of tissue specimens contains 33 samples from Han,Miao and Buyi ethnics, respectively.We analyze the expression of SBEM in different mammary tissues in different ethnics and the association of different SBEM expression levels in tissue of TNBC patients with clinical- pathological features, DFS and OS in Han,Miao and Buyi ethnics,respectively. Results: SBEM expression in breast cancer tumor cells were related to the ki67 in the Han, Miao and Buyi ethnic ( P =0.034、0.027、0.047), respectively. There was a marked associations between the SBEM expression level and lymphatic metastasis ( P = 0.042、0.039) in the Han and Miao ethnic, while the same results were not found in the Buyi people ( P =0.072).There was significant difference in DFS ( P =0.028、0.013)and OS ( P =0.09、0.037) between the high expression group and low expression group in the Han and Miao ethnic.But there was no significant difference in DFS ( P = 0.053 ) and OS ( P = 0.088 )in the Buyi people. Conclusion: The SBEM positive detection rate was no significant difference in the han, miao and buyi ethnic groups. SBEM was associated with DFS and OS in the Han and Miao ethnic, while no correlation in the Buyi ethnic. Pathology small breast epithelial mucin breast cancer DFS OS ethnic difference Figures Figure 1 Figure 2 Figure 3 Introduction Breast cancer is the most common malignancy and is second only to lung cancer in mortality among women worldwide [ 1 , 2 ] .While the incidence rate of breast cancer continues to rise over the last few decades, its mortality rate,on the other other hand, declines every year thanks for the development of diagnosis and targeting medication [ 3 , 4 ] .Triple-negative breast cancer (TNBC), one of five molecular subtypes recognized in 2000 [ 5 , 6 ] , lacks estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression.TNBC is characterized by high incidence in young women, early recurrence and shows a relative sensitivity of chemotherapy. Most studies [ 7 – 9 ] showed that the prognosis of TNBC was less favorable than that of non-TNBC. Micro metastasis is considered to be a key factor for poor prognosis of breast cancer patients [ 10 ] .Despite the improvement in detection of breast cancer,about 30% of patients are still detected with micro metastasis at their first visit.The micro metastasis of breast cancer before primary treatment is considered to be one of the recurrence reasons that will directly impact the survival of patients.The development of distant metastasis is the major cause of their death [ 11 ] .So,it is crucial to find specific markers to detected micro metastasis and provide useful information to guide early therapeutic methods of breast cancer patients,especially TNBC. Small breast epithelial mucin (SBEM) was a tissue specific protein and only expresses in mammary and salivary glands [ 12 ] .High SBEM expression was found to be strongly associated with the histopathological detection of lymph node metastasis [ 12 ] . SBEM could serve as a useful marker for breast micro metastasis,also as a specific targets for the treatment of breast cancer [ 12 ] . O 'brien [ 13 ] confirmed that rates of detection of SBEM in protein levels were 51% (52/103) and 4% (1/26) in breast cancer and non-breast cancer tissue, respectively, which further confirmed the SBEM expression was significantly higher in breast cancer tissue than non-breast tissue.Skliris GP [ 14 ] study showed that SBEM expression rate was 18% in 300 patients with breast cancer using the method of immunohistochemical analysis and the SBEM expression rate was significantly higher in ER negative(22%) than in ER positive (13%) breast cancer tissue.Several laboratories showed that SBEM expression correlated with higher tumor grade,TNM staging and lymph node metastasis at both mRNA and protein levels. SBEM has significant guidance for clinical activities. Liu ZZ [ 15 ] reported that SBEM has the potential to be a specific marker for predicting hematogenous micro metastasis and response to neo-adjuvant chemotherapy in breast cancer.Valladares-Ayerbes M et al. [ 16 ] studied the expression profiles of SBEM gene in silico and in vitro, and demonstrated that SBEM-mRNA could serve as a marker for bone marrow micro metastasis in breast cancer patients and SBEM-mRNA could serve as a marker for bone marrow micro metastasis in breast cancer patients [ 15 ] .Research of Liang Liu et al [ 17 ] suggested SBEM 3 + score was cut-off value of prognosis and significantly correlated with decreased DFS and OS in TNBC patients.SBEM is an independent risk predictor and may offer utility as a prognostic marker in TNBC patients [ 17 ] . Based on the resules above,SBEM might play an important role in progression and metastasis of breast cancer indifferent races, especially in TNBC. But humans have genetic diversity and every race and nationality's genome has its own characteristics. Only to figure out what each nation's genetic structure characteristics and the change rule, we can analyze their origins and the genetic relationship with other ethnic groups.This kind of population genetics research is a difficult project.The genetics investigation need to rely on all sorts of genetic markers, especially those with racial specificity and individual specific genetic markers,which can provide enough valuable genetic information. The Southern GuiZhou is a multi-ethnic area of China,of which Han, Miao and Buyi ethnics are its main components. The breast cancer incidence here is increasing year by year as well as other regions in China. Because the different ethnic groups have different genetic background and ways of life, We are not sure whether there is difference between different ethnic groups, including the SBEM expression level and the prognostic significance in TNBC.And to the best of our knowledge,this is the first study to investigate the differences of the expression of SBEM in mammary tissue of Han,Miao and Buyi ethnic and prognosis in TNBC patients in different ethnics.The aim of this study was to analyze whether there is the same expression, prediction results or the clinical meaning for SBEM in different ethnics. Materials And Methods The study examined cases from 297 patients diagnosed from 2014 to 2015 in Third Affiliated Hospital of Guizhou Medical University ,including 99 normal breast tissue specimens, 99 cases of breast benign tumor tissue specimens and 99 available formalin-fixed paraffin-embedded tissues specimens from TNBC patients by means of immunohistochemistry(IHC).Each set of tissue specimens contains 33 samples from Han,Miao and Buyi ethnics, respectively.Clinical data of all the cases were reviewed retrospectively from medical records in our hospital. All patients were females and had a minimum 4 years’ follow-up records.The follow-up period end at 2020.06.30. All the TNBC patients underwent operational treatment according to clinical practice guidelines of National Comprehensive Cancer Network (NCCN) of the United States. None of the patients received neoadjuvant therapy. Statistic and analysis of clinicopathological parameters, including age at diagnosis, disease stage,tumor size, tumor grade, lymph node status ,P53and Ki67,were listed in Table 2 – 4 . All TNBC cases examined were ER and PR negative by IHC. HER2 status was considered negative if the immunohistochemical score was 0 or 1+, or if the score was 2 + but non-amplification by fluorescence in situ hybridization (FISH), and positive if the score was 3+. Based on the past research results, SBEM expression with SBEM 3 + score is the SBEM cut-off value of prognosis. We divided the cases into two groups, one is the SBEM < 3 + group defined as a high expression group,the other is SBEM = 3 + group defined as a high expression group. The study examined cases from 297 patients diagnosed from 2014 to 2015 in Third Affiliated Hospital of Guizhou Medical University ,including 99 normal breast tissue specimens, 99 cases of breast benign tumor tissue specimens and 99 available formalin-fixed paraffin-embedded tissues specimens from TNBC patients by means of immunohistochemistry(IHC).Each set of tissue specimens contains 33 samples from Han,Miao and Buyi ethnics, respectively.Clinical data of all the cases were reviewed retrospectively from medical records in our hospital. All patients were females and had a minimum 4 years’ follow-up records.The follow-up period end at 2020.06.30. All the TNBC patients underwent operational treatment according to clinical practice guidelines of National Comprehensive Cancer Network (NCCN) of the United States. None of the patients received neoadjuvant therapy. Statistic and analysis of clinicopathological parameters, including age at diagnosis, disease stage,tumor size, tumor grade, lymph node status ,P53and Ki67,were listed in Table 2 – 4 . All TNBC cases examined were ER and PR negative by IHC. HER2 status was considered negative if the immunohistochemical score was 0 or 1+, or if the score was 2 + but non-amplification by fluorescence in situ hybridization (FISH), and positive if the score was 3+. Based on the past research results, SBEM expression with SBEM 3 + score is the SBEM cut-off value of prognosis. We divided the cases into two groups, one is the SBEM < 3 + group defined as a high expression group,the other is SBEM = 3 + group defined as a high expression group. Sbem Expression And Evaluation Of Ihc All tissues were collected surgically under the supervision of an experienced pathologist. SBEM expression was measured by IHC. Streptavidinperosidase (S-P) IHC staining was performed using SBEM antibody of mouse monoclonal (diluted 1/800, Abcam plc. Cambridge, UK). The detailed procedures were done as described by Jennbacken [ 18 ] . PBS was used to replace the primary antibody in negative controls. SBEM was a secreted protein and it was mainly located in cell membrane, secondly in cytoplasm. Normal breast tissues were in general weakly or negative. So it was evaluated and scored if cell membrane and/or cytoplasm reactivity were observed [ 8 ] . According to our data and TMA IHC grading method by Serrero G [ 19 ] Pan [ 20 ] and Liu Liang [ 17 ] , our scoring was semiquantitatively categorized as: ≤5% of tumor cells staining with/without weakly stained was negative (0), followed by a score of 1 (> 5% of tumor cells and with weak/focal positive staining or ≤ 5% of tumor cells with strongly stained), 2 (> 5% of tumor cells and with moderate/focal positive staining), 3 (> 5% of tumor cells and with strong/diffuse positive staining). Statistical analysis The correlation between SBEM, Clinicopathological characteristics and survival outcomes was compared by Pearson’s Χ 2 test. Survival analyses, including DFS and OS, were performed with the log rank test and all results were displayed in Kaplan–Meier. DFS was defined as the time interval from date of diagnosis to the time of last disease free follow-up or at death for those patients who died without a previous recurrence [ 21 ] . OS was defined as the time interval from date of diagnosis to time of last follow-up or death [ 21 ] . Statistical significance was defined as P value < 0.05. SPSS17.0 software package was used for all statistical analyses. Results Figure 1 Immunohistochemical staining for SBEM. A: 0+: ≤5% of tumor cells staining with/without weakly stained was negative (original magnification × 200); B: 1+: >5% of tumor cells and with weak/focal positive staining or ≤ 5% of tumor cells with strongly stained (original magnification × 100); C: 2+: >5% of tumor cells and with moderate/focal positive staining (original magnification × 200); D: 3+: >5% of tumor cells and with strong/diffuse positive staining (original magnification × 200). Table 1 showed the SBEM positive detection rate in the breast cancer tissue, breast benign tumor tissue and normal breast tissue in the han, miao and buyi ethnic(Table 1 ).SBEM positive detection rate of breast cancer tissue is significantly higher than the breast benign tumor tissue and normal breast tissue ( P = 0.005). But there was no significant difference in the han, miao and buyi ethnic in breast cancer tissue, breast benign tumor tissue and normal breast tissue( P > 0.05 )( Table 1 ). Table 1 SBEM positive detection rate in the breast cancer tissue, breast benign tumor tissue and normal breast tissue in the han, miao and buyi ethnic Tissue type SBEM positive detection rate (%) Han ethnic Miao ethnic Buyi ethnic P 值 Breast cancer tissue 49 47 45 0.982 Breast benign tumor tissue 4 3 3 0.923 Normal breast tissue 3 2 2 0.889 P 值 0.005 0.005 0.005 The clinicopathological characteristics of patients were described in Table 2 – 4 . SBEM expression in TNBC tumor cells were related to ki67 in the Han, Miao and Buyi ethnic ( P = 0.034、0.027、0.047), respectively. There was a marked association between the low expression of SBEM group and high expression group in lymphatic metastasis ( P = 0.042、0.039) in the Han and Miao ethnic, while the same results were not found in the Buyi people ( P = 0.072 )(Table 2 , 3 , 4 ). Table 2 Clinicopathological characteristics of patients in Han ethnic Parameter Number (n) Subgroup cut-offs SBEM 35 X ≤ 35 26 19 7 73.1 26.9 7 4 3 57.1 42.8 0.614 TNM staging 33 Ⅰ(1) Ⅱ(2) Ⅲ(3) 26 6 14 6 23.1 53.8 23.1 7 1 3 3 14.3 42.8 42.8 0.075 P53 31 Mutated No-mutated 24 11 13 45.8 44.2 7 4 3 57.1 42.8 0.801 Lymph Node 33 + 26 10 16 38.5 61.5 7 5 2 71.4 28.6 0.042 Grade 30 Low (1) Mod(2) High(3) 23 9 8 6 39.1 34.8 26.1 7 2 3 2 28.6 42.8 28.6 0.212 Size 33 X > 20 mm X ≤ 20 mm 26 14 12 53.8 46.2 7 4 3 57.1 42.8 0.872 Ki67 32 X > 35 X ≤ 35 26 11 15 42.3 57.7 6 5 1 83.3 16.7 0.034 Table 3 Clinicopathological characteristics of patients in Miao ethnic Parameter Number (n) Subgroup cut-offs SBEM 35 X ≤ 35 26 22 4 84.6 15.4 7 5 2 71.4 28.6 0.523 TNM staging 33 Ⅰ(1) Ⅱ(2) Ⅲ(3) 26 7 13 6 26.9 53.8 19.3 7 1 4 2 14.3 63.6 28.6 0.092 P53 27 Mutated No-mutated 21 10 11 47.6 52.4 6 3 3 50.0 50.0 0.901 Lymph Node 33 + 26 11 15 42.3 57.7 7 6 1 85.7 14.3 0.039 Grade 30 Low (1) Mod(2) High(3) 24 9 8 7 37.5 33.3 29.2 6 2 2 2 33.3 33.3 33.3 0.361 Size 33 X > 20 mm X ≤ 20 mm 26 17 9 65.4 34.6 7 4 3 63.6 36.4 0.849 Ki67 31 X > 35 X ≤ 35 24 7 17 19.2 70.8 7 5 2 71.4 28.6 0.027 Table 4 Clinicopathological characteristics of patients in Buyi ethnic Parameter Number (n) Subgroup cut-offs SBEM 35 X ≤ 35 25 21 4 72.4 27.6 8 6 2 63.6 36.4 0.806 TNM staging 33 Ⅰ(1) Ⅱ(2) Ⅲ(3) 25 6 12 8 24.0 48.0 32.0 8 1 3 4 12.5 37.5 50.0 0.101 P53 29 Mutated No-mutated 22 13 9 59.1 40.9 7 4 3 63.6 36.4 0.678 Lymph Node 33 + 25 10 15 40.0 60.0 8 5 3 62.5 37.5 0.072 Grade 26 Low (1) Mod(2) High(3) 20 8 7 5 40.0 35.0 25.0 6 3 2 1 50.0 33.3 16.7 0.201 Size 33 X > 20 mm X ≤ 20 mm 25 14 12 56.0 44.0 8 5 3 62.5 37.5 0.615 Ki67 30 X > 35 X ≤ 35 23 9 14 39.1 60.9 7 4 3 63.6 36.4 0.047 Figure 2 Kaplan-Meier estimates for DFS by SBEM scores in Han, Miao and Buyi ethnic Figure 3 Kaplan-Meier estimates for OS by SBEM scores in Han, Miao and Buyi ethnic Discussion Breast cancer is pushed into first place in the United States and many other parts of world.Breast cancer alone is expected to account for 29% (226,870) of all new cancer cases among women [ 22 ] .Although incidence rate of breast cancer remains relatively stable in recent 5 years,its death rate declines by 34% because of the development of diagnosis and targeting medication [ 4 , 10 ] .The micro metastasis of breast cancer before primary treatment is considered to be one of the recurrence reasons that will directly impact the survival of patients.So,it is crucial to find specific markers to detected micro metastasis and provide useful information to guide early therapeutic methods of TNBC patients. The definition of tumor markers is broad.Tumor cells may express certain molecules at a different rate from that of normal cells,and these substances are released in the bloodstream or in other biologic fluids.Although various biological markers had been proposed for the detection of breast cancer cells,they were often affected by tumor differentiation,lower specificity and detection rate. But almost all the current clinical application of tumor markers can not reach ideal level in the identification of the tumor specificity and sensitivity, especially in TNBC at present. SBEM was a tissue specific protein, a member of the MUC family, and its expression is highly specific to mammary gland tissue.High SBEM expression was found to be strongly associated with the histopathological detection of lymph node metastasis [ 12 ] .SBEM was a secreted protein and it was mainly located in cell membrane.Normal breast tissues were in general weakly or negative.SBEM could serve as a useful marker for breast micro metastasis,also as a specific targets for the treatment of breast cancer [ 12 ] . However,as the genomes of different races and nationalities have their own characteristics,it is of guiding significance to explore the genetic characteristics of different ethnics in the diagnosis and treatment of TNBC.The Buyi and Miao ethnic groups are the main components in Guizhou province in China.With different genetic backgrounds and lifestyles from those of the Han ethnic.As far as we knew the difference in the expression level of SBEM among different ethnic groups and its prognosis significance for survival have not been reported.The aim of this research was to analyze whether there is the same expression in different mammary tissues in different ethnics and the association of SBEM expression in tissue of TNBC patients with clinical- pathological features, DFS and OS, and to identify whether there is the same prediction results or the clinical meaning for SBEM in Han,Miao and Buyi ethnics. Researchers have conducted many studies on SBEM as a tumor marker of breast cancer micro metastasis worldwide.RT-PCR and immunohistochemistry are used to detect the expression of gene and protein nowadays [ 15 , 23 ] .The research of O'Brien et al [ 13 ] has shown that SBEM are expressed relatively exclusively in breast tissue than non-breast tissue and are potential new markers for breast cancer [ 14 ] .Skliris GP [ 14 ] study showed that the SBEM expression rate was significantly higher in ER negative(22%) than in ER positive (13%) breast cancer tissue.Zhong Lei et al [ 24 ] study showed that SBEM expression rate was 53.3% in 60 patients with breast cancer the negative SBEM- mRNA resules were found in peripheral blood in 20 patients with mammary gland fibroma and 10 cases of healthy people. SBEM expression in TNBC tumor cells were related to TNM staging and axillary lymph node metastasis. The similar results were found by Yang Hua-wei et al [ 25 ] .This research shows that SBEM is mainly expressed in the cell membrane, the second expression in the cytoplasm, few expression in the nucleus. SBEM positive detection rate of breast cancer tissue is significantly higher than the breast benign tumor tissue and normal breast tissue. But there was no significant difference in the han, miao, buyi ethnic in breast cancer tissue, breast benign tumor tissue and normal breast tissue. Many factors can affect the prognosis of breast cancer recurrence and death, including tumor histologic features, clinical and pathological features of primary tumor, lymph node status, tumor hormone levels,Her-2 state, complications, age, menopausal status, tumor size, tumor grade, TNM staging, Ki67 and P53, which can evaluate DFS and OS [ 26 – 27 ] . Ki67 is also a important marker of cell proliferation, and it has important significance for prognosis judgment in breast cance [ 28 ] . In our study, SBEM expression in TNBC tumor cells were related to the ki67 in the Han, Miao and Buyi ethnic ( P = 0.034、0.027、0.047), respectively. There was a marked associations between the low expression of SBEM group and high expression group in lymphatic metastasis ( P = 0.042、0.039) in the Han and Miao ethnic, while the same results were not found in the Buyi people ( P = 0.072)).Thus it can be seen that there is difference in different ethnic groups between SBEM different expression levels and metastatic tumor recurrence and the prognosis. The past studies have shown that SBEM correlated with the prognosis of patients. Breast cancer stem cell scan obtain higher resistance and high invasive due to their high plasticity [ 29 ] . The previous studies have not been reported whether there is the same prediction results or the clinical meaning for the same tumor marker in different ethnics.The experiment has carried on the preliminary exploration to this. In our study, we found that DFS and OS function curves showed the large separation between the high expression group and low expression group. There was significant difference in DFS ( P = 0.028、0.013)and OS ( P = 0.09、0.037)between the high expression group and low expression group in the Han and Miao ethnic.But there was no significant difference in DFS ( P = 0.053 ) and OS ( P = 0.088 )in the Buyi people.Thus it can be seen there is different prognostic significance in different ethnic groups for SBEM different expression levels. In conclusion, this research shows that SBEM positive detection rate was no significant difference in the han, miao and buyi ethnic in breast cancer tissue, breast benign tumor tissue and normal breast tissue.The SBEM expression level is related to the prognosis of TNBC patients and its clinical significance is not exactly the same in different ethnics ,which can provide a more reasonable choice for clinical individualized treatment and prognostic judgement and reduce a certain amount of medical costs. However, it needs more centers to participate in further study because this is just a retrospective single-center study and the small sample size limits to some extent the generalization of the findings made in the study. Conclusion We have demonstrated that the SBEM positive detection rate was no significant difference in the han, miao and buyi ethnic groups in breast cancer tissue, breast benign tumor tissue and normal breast tissue.The expression of SBEM does significantly correlate with a DFS and an OS of TNBC patients in the han, miao and buyi ethnic. But it is not obvious for prognostic significance in Buyi ethnic.The distinction in different ethnic groups shall certainly provide a more reasonable choice for clinical individualized treatment and prognostic judgement in TNBC patients. Abbreviations SBEM: Small breast epithelial mucin; TNBC: Triple-negative breast cancer;DFS: Disease-free survival; OS: Overall survival; ER: Estrogen receptor; PR: Progesterone receptor; HER2: Human epidermal growth factor receptor-2; TNM: Tumor node metastasis; IHC: immunohistochemical; PB: Peripheral blood; RT–PCR: Reverse transcription polymerase chain reaction; FISH: Fluorescence in situhybridization; NCCN: National comprehensive cancer network; CEA: Carcinoembryonic antigen. Declarations Consent Written informed consent was obtained from the patient for publication of this report and any accompanying images. Competing interests The authors declare that they have no competing interests. Authors’ contributions LL contributed to the study design, data acquisition and analysis and drafted the manuscript; WL was involved in data acquisition and revision of the manuscript; QL and YY worked on aspects of data acquisition and analysis; HY contributed to the study design and data-analysis, developed the algorithm and coordinated the study; LH conceived and coordinated the study. All authors read and approved the final manuscript. Acknowledgments We thank Dr. Xie Xiaodogn and Dr. Jing Peng for expert technical assistance with IHC. We thank Dr. Yang Jie, Dr. Liu Hui and Dr. You Hui for secretarial and organizational support in our experiments. We also thank Dr. Liu Hongshuo and Dr. Wang Xu for critical revision of the manuscript. Author details Department of Oncology, Third Affiliated Hospital of Guizhou Medical University References [1] Siegel R L, Miller K D,Jemal A.Cancer statistics,2020［J］.CA Cancer J Clin,2020,70(1):7-30. 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[23] Wu Fanglan, Fan Chengxian.SBEM mRNA detection and its clinical meaning inbreast cancer patients with bone marrow. Modern Chinese medicine. 2009, 22(19): 3473-3476. [24] Zhong Lei, Zhang Jianguo, Guo Baoliang, et al . The clinical significance of the peripheral blood expression of SBEM - mRNA and CEA in breast cancer patients.Chinese journal of clinical oncology, 2008,35(23): 1344-1347. [25] Yang HW, Cao J, Yang NW, et, al . Expression of small breast epithelial mucin mRNA in peripheral blood of breast cancer patients and its clinical significance. Ai Zheng. 2005, 24(7), 842-845. [26] Ravdin PM, Siminoff LA, et al . Computer program to assist in making decision about adjuvant therapy for women with early breast cancer. J Clin Oncol 2001, 19: 980-991. [27] Olivotto IA, Bajdik CD, Ravdin PM, e t al. Population-Based Validation of thePrognostic Model Adjuvant for early breast cancer. J Clin Oncol 2005, 23: 2716-2725. [28] Weigel MT, Dowsett M. Current and emerging biomarkers in breast cancer: prognosis and prediction. Endocrine-Related Cancer 2010, 17: R245-262. [29] Lindstrom L S,Yau, C,Czene K,et al.Intratumor heterogeneity of the estrogen eceptor and the long-term risk of fatal breast cancer［J］.J Natl Cancer Inst, 2018,110(7):726-733. 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. 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-56422","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research","associatedPublications":[],"authors":[{"id":1330942,"identity":"5f7c626e-249a-41c5-bee1-537e7657387c","order_by":0,"name":"Liu Liang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAzklEQVRIiWNgGAWjYBACxmYGBmYY+0FCRQ3RWgxAbGaDB2eOEWcTTAub5MMWZkKKgcrbeQ9/Lqj5I28ukXysIrGBjYG/vTuBgMP40qRnHDMw3DkjLe1G4g4ZBokzZzcQ0MJjxszDZsC44XaO2Y3EM2wMBhK5BLUYf+b5Z2AP0lKQ2MZMlBYDad42g0SQFgZitZhJ8/YZJ2+4/yxZIuHMMR6CfjHsPwN02Dc52w1nDh/8+KOiRo6/vZeAlgY0AR68ykFAnqCKUTAKRsEoGAUAW15FNeJHvtMAAAAASUVORK5CYII=","orcid":"","institution":"Third Affiliated Hospital of Guizhou Medical University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Liu","middleName":"","lastName":"Liang","suffix":""},{"id":1330943,"identity":"4382d27d-8439-4364-9a5b-1601c276ef2a","order_by":1,"name":"Ye Weilin","email":"","orcid":"","institution":"Third Affiliated Hospital of Guizhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ye","middleName":"","lastName":"Weilin","suffix":""},{"id":1330944,"identity":"644a3183-88ce-4e08-8847-20b5d014a62c","order_by":2,"name":"Liu Hui","email":"","orcid":"","institution":"Third Affiliated Hospital of Guizhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Liu","middleName":"","lastName":"Hui","suffix":""},{"id":1330945,"identity":"44fbc521-de47-4a23-bfff-40f5d5da5e4b","order_by":3,"name":"Lu Qili","email":"","orcid":"","institution":"Third Affilitiaed Hospital of Guizhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lu","middleName":"","lastName":"Qili","suffix":""},{"id":1330946,"identity":"1627603f-5d5b-47a7-81ec-33529dc7e185","order_by":4,"name":"Wang Jun","email":"","orcid":"","institution":"Third Affiliated Hospital of Guizhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Wang","middleName":"","lastName":"Jun","suffix":""},{"id":1330947,"identity":"0c75735e-7766-47a5-acba-49e8511fda49","order_by":5,"name":"Yang Yan","email":"","orcid":"","institution":"Third Affiliated Hospital of Guizhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Yan","suffix":""},{"id":1330948,"identity":"1712bec6-648b-47dd-b09b-9580d489c29e","order_by":6,"name":"He Yang","email":"","orcid":"","institution":"Third Affiliated Hospital of Guizhou Medical University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"He","middleName":"","lastName":"Yang","suffix":""}],"badges":[],"createdAt":"2020-08-09 12:41:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-56422/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-56422/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":1882949,"identity":"519c46d9-1c59-45f7-bc27-498482f2837b","added_by":"auto","created_at":"2020-08-11 17:59:15","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":120767,"visible":true,"origin":"","legend":"Immunohistochemical staining for SBEM. A: 0+: ≤5% of tumor cells staining with/without weakly stained was negative (original magnification × 200); B: 1+: \u003e5% of tumor cells and with weak/focal positive staining or ≤5% of tumor cells with strongly stained (original magnification × 100); C: 2+: \u003e5% of tumor cells and with moderate/focal positive staining (original magnification × 200); D: 3+: \u003e5% of tumor cells and with strong/diffuse positive staining (original magnification × 200).","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-56422/v1/1.jpg"},{"id":1882950,"identity":"6df5cb0d-6c79-49ef-b4af-f58c444fd60d","added_by":"auto","created_at":"2020-08-11 17:59:15","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":31632,"visible":true,"origin":"","legend":"Kaplan-Meier estimates for DFS by SBEM scores in Han, Miao and Buyi ethnic","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-56422/v1/2.jpg"},{"id":1882951,"identity":"3c975f9e-1c96-4824-a24f-cb610578950e","added_by":"auto","created_at":"2020-08-11 17:59:15","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":30354,"visible":true,"origin":"","legend":"Kaplan-Meier estimates for OS by SBEM scores in Han, Miao and Buyi ethnic ","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-56422/v1/3.jpg"},{"id":13574087,"identity":"8a12b188-c09c-4cdf-9497-0b1d3fc4443b","added_by":"auto","created_at":"2021-09-17 03:57:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":427900,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-56422/v1/d50c9da3-5eeb-4185-90ce-67434ef122ff.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eStudy on\u0026nbsp;the small breast epithelial mucin tumor tissue expression difference\u0026nbsp;and\u0026nbsp;its relationship with survival in\u0026nbsp;triple-negative\u0026nbsp;breast cancer\u0026nbsp;patients in\u0026nbsp;Han, Miao and Buyi ethnic\u003c/p\u003e","fulltext":[{"header":"Introduction","content":" \u003cp\u003eBreast cancer is the most common malignancy and is second only to lung cancer in mortality among women worldwide \u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e.While the incidence rate of breast cancer continues to rise over the last few decades, its mortality rate,on the other other hand, declines every year thanks for the development of diagnosis and targeting medication\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e.Triple-negative breast cancer (TNBC), one of five molecular subtypes recognized in 2000 \u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e, lacks estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression.TNBC is characterized by high incidence in young women, early recurrence and shows a relative sensitivity of chemotherapy. Most studies \u003csup\u003e[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e showed that the prognosis of TNBC was less favorable than that of non-TNBC.\u003c/p\u003e \u003cp\u003eMicro metastasis is considered to be a key factor for poor prognosis of breast cancer patients\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.Despite the improvement in detection of breast cancer,about 30% of patients are still detected with micro metastasis at their first visit.The micro metastasis of breast cancer before primary treatment is considered to be one of the recurrence reasons that will directly impact the survival of patients.The development of distant metastasis is the major cause of their death\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.So,it is crucial to find specific markers to detected micro metastasis and provide useful information to guide early therapeutic methods of breast cancer patients,especially TNBC.\u003c/p\u003e \u003cp\u003eSmall breast epithelial mucin (SBEM) was a tissue specific protein and only expresses in mammary and salivary glands\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e.High SBEM expression was found to be strongly associated with the histopathological detection of lymph node metastasis\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. SBEM could serve as a useful marker for breast micro metastasis,also as a specific targets for the treatment of breast cancer\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. O 'brien\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003econfirmed that rates of detection of SBEM in protein levels were 51% (52/103) and 4% (1/26) in breast cancer and non-breast cancer tissue, respectively, which further confirmed the SBEM expression was significantly higher in breast cancer tissue than non-breast tissue.Skliris GP\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003estudy showed that SBEM expression rate was 18% in 300 patients with breast cancer using the method of immunohistochemical analysis and the SBEM expression rate was significantly higher in ER negative(22%) than in ER positive (13%) breast cancer tissue.Several laboratories showed that SBEM expression correlated with higher tumor grade,TNM staging and lymph node metastasis at both mRNA and protein levels.\u003c/p\u003e \u003cp\u003eSBEM has significant guidance for clinical activities. Liu ZZ\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e reported that SBEM has the potential to be a specific marker for predicting hematogenous micro metastasis and response to neo-adjuvant chemotherapy in breast cancer.Valladares-Ayerbes M et al. \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e studied the expression profiles of SBEM gene in silico and in vitro, and demonstrated that SBEM-mRNA could serve as a marker for bone marrow micro metastasis in breast cancer patients and SBEM-mRNA could serve as a marker for bone marrow micro metastasis in breast cancer patients \u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e.Research of Liang Liu et al \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003esuggested SBEM 3\u0026thinsp;+\u0026thinsp;score was cut-off value of prognosis and significantly correlated with decreased DFS and OS in TNBC patients.SBEM is an independent risk predictor and may offer utility as a prognostic marker in TNBC patients \u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eBased on the resules above,SBEM might play an important role in progression and metastasis of breast cancer indifferent races, especially in TNBC. But humans have genetic diversity and every race and nationality's genome has its own characteristics. Only to figure out what each nation's genetic structure characteristics and the change rule, we can analyze their origins and the genetic relationship with other ethnic groups.This kind of population genetics research is a difficult project.The genetics investigation need to rely on all sorts of genetic markers, especially those with racial specificity and individual specific genetic markers,which can provide enough valuable genetic information.\u003c/p\u003e \u003cp\u003eThe Southern GuiZhou is a multi-ethnic area of China,of which Han, Miao and Buyi ethnics are its main components. The breast cancer incidence here is increasing year by year as well as other regions in China. Because the different ethnic groups have different genetic background and ways of life, We are not sure whether there is difference between different ethnic groups, including the SBEM expression level and the prognostic significance in TNBC.And to the best of our knowledge,this is the first study to investigate the differences of the expression of SBEM in mammary tissue of Han,Miao and Buyi ethnic and prognosis in TNBC patients in different ethnics.The aim of this study was to analyze whether there is the same expression, prediction results or the clinical meaning for SBEM in different ethnics.\u003c/p\u003e "},{"header":"Materials And Methods","content":" \u003cp\u003eThe study examined cases from 297 patients diagnosed from 2014 to 2015 in Third Affiliated Hospital of Guizhou Medical University ,including 99 normal breast tissue specimens, 99 cases of breast benign tumor tissue specimens and 99 available formalin-fixed paraffin-embedded tissues specimens from TNBC patients by means of immunohistochemistry(IHC).Each set of tissue specimens contains 33 samples from Han,Miao and Buyi ethnics, respectively.Clinical data of all the cases were reviewed retrospectively from medical records in our hospital. All patients were females and had a minimum 4 years\u0026rsquo; follow-up records.The follow-up period end at 2020.06.30. All the TNBC patients underwent operational treatment according to clinical practice guidelines of National Comprehensive Cancer Network (NCCN) of the United States. None of the patients received neoadjuvant therapy. Statistic and analysis of clinicopathological parameters, including age at diagnosis, disease stage,tumor size, tumor grade, lymph node status ,P53and Ki67,were listed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. All TNBC cases examined were ER and PR negative by IHC. HER2 status was considered negative if the immunohistochemical score was 0 or 1+, or if the score was 2\u0026thinsp;+\u0026thinsp;but non-amplification by fluorescence in situ hybridization (FISH), and positive if the score was 3+. Based on the past research results, SBEM expression with SBEM 3\u0026thinsp;+\u0026thinsp;score is the SBEM cut-off value of prognosis. We divided the cases into two groups, one is the SBEM\u0026thinsp;\u0026lt;\u0026thinsp;3\u0026thinsp;+\u0026thinsp;group defined as a high expression group,the other is SBEM\u0026thinsp;=\u0026thinsp;3\u0026thinsp;+\u0026thinsp;group defined as a high expression group.\u003c/p\u003e \n\u003cp\u003eThe study examined cases from 297 patients diagnosed from 2014 to 2015 in Third Affiliated Hospital of Guizhou Medical University ,including 99 normal breast tissue specimens, 99 cases of breast benign tumor tissue specimens and 99 available formalin-fixed paraffin-embedded tissues specimens from TNBC patients by means of immunohistochemistry(IHC).Each set of tissue specimens contains 33 samples from Han,Miao and Buyi ethnics, respectively.Clinical data of all the cases were reviewed retrospectively from medical records in our hospital. All patients were females and had a minimum 4 years\u0026rsquo; follow-up records.The follow-up period end at 2020.06.30. All the TNBC patients underwent operational treatment according to clinical practice guidelines of National Comprehensive Cancer Network (NCCN) of the United States. None of the patients received neoadjuvant therapy. Statistic and analysis of clinicopathological parameters, including age at diagnosis, disease stage,tumor size, tumor grade, lymph node status ,P53and Ki67,were listed in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. All TNBC cases examined were ER and PR negative by IHC. HER2 status was considered negative if the immunohistochemical score was 0 or 1+, or if the score was 2\u0026thinsp;+\u0026thinsp;but non-amplification by fluorescence in situ hybridization (FISH), and positive if the score was 3+. Based on the past research results, SBEM expression with SBEM 3\u0026thinsp;+\u0026thinsp;score is the SBEM cut-off value of prognosis. We divided the cases into two groups, one is the SBEM\u0026thinsp;\u0026lt;\u0026thinsp;3\u0026thinsp;+\u0026thinsp;group defined as a high expression group,the other is SBEM\u0026thinsp;=\u0026thinsp;3\u0026thinsp;+\u0026thinsp;group defined as a high expression group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSbem Expression And Evaluation Of Ihc\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll tissues were collected surgically under the supervision of an experienced pathologist. SBEM expression was measured by IHC. Streptavidinperosidase (S-P) IHC staining was performed using SBEM antibody of mouse monoclonal (diluted 1/800, Abcam plc. Cambridge, UK). The detailed procedures were done as described by Jennbacken \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. PBS was used to replace the primary antibody in negative controls. SBEM was a secreted protein and it was mainly located in cell membrane, secondly in cytoplasm. Normal breast tissues were in general weakly or negative. So it was evaluated and scored if cell membrane and/or cytoplasm reactivity were observed \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. According to our data and TMA IHC grading method by Serrero G \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e Pan \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e and Liu Liang \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e, our scoring was semiquantitatively categorized as: \u0026le;5% of tumor cells staining with/without weakly stained was negative (0), followed by a score of 1 (\u0026gt;\u0026thinsp;5% of tumor cells and with weak/focal positive staining or \u0026le;\u0026thinsp;5% of tumor cells with strongly stained), 2 (\u0026gt;\u0026thinsp;5% of tumor cells and with moderate/focal positive staining), 3 (\u0026gt;\u0026thinsp;5% of tumor cells and with strong/diffuse positive staining).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\n\u003cp\u003eThe correlation between SBEM, Clinicopathological characteristics and survival outcomes was compared by Pearson\u0026rsquo;s \u0026Chi;\u003csup\u003e2\u003c/sup\u003e test. Survival analyses, including DFS and OS, were performed with the log rank test and all results were displayed in Kaplan\u0026ndash;Meier. DFS was defined as the time interval from date of diagnosis to the time of last disease free follow-up or at death for those patients who died without a previous recurrence \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. OS was defined as the time interval from date of diagnosis to time of last follow-up or death\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e. Statistical significance was defined as \u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05. SPSS17.0 software package was used for all statistical analyses.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eFigure \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e Immunohistochemical staining for SBEM. A: 0+: \u0026le;5% of tumor cells staining with/without weakly stained was negative (original magnification\u0026thinsp;\u0026times;\u0026thinsp;200); B: 1+: \u0026gt;5% of tumor cells and with weak/focal positive staining or \u0026le;\u0026thinsp;5% of tumor cells with strongly stained (original magnification\u0026thinsp;\u0026times;\u0026thinsp;100); C: 2+: \u0026gt;5% of tumor cells and with moderate/focal positive staining (original magnification\u0026thinsp;\u0026times;\u0026thinsp;200); D: 3+: \u0026gt;5% of tumor cells and with strong/diffuse positive staining (original magnification\u0026thinsp;\u0026times;\u0026thinsp;200).\u003c/p\u003e\n\u003cp\u003eTable\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e showed the SBEM positive detection rate in the breast cancer tissue, breast benign tumor tissue and normal breast tissue in the han, miao and buyi ethnic(Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).SBEM positive detection rate of breast cancer tissue is significantly higher than the breast benign tumor tissue and normal breast tissue (\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.005). But there was no significant difference in the han, miao and buyi ethnic in breast cancer tissue, breast benign tumor tissue and normal breast tissue( \u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05 )( Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eSBEM positive detection rate in the breast cancer tissue, breast benign tumor tissue and normal breast tissue in the han, miao and buyi ethnic\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTissue type\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"4\" align=\"left\"\u003e\n\u003cp\u003eSBEM positive detection rate (%)\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eHan ethnic\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eMiao ethnic\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eBuyi ethnic\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e值\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBreast cancer tissue\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e49\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e47\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.982\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eBreast benign tumor tissue\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.923\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eNormal breast tissue\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.889\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e值\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e0.005\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe clinicopathological characteristics of patients were described in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e. SBEM expression in TNBC tumor cells were related to ki67 in the Han, Miao and Buyi ethnic (\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.034、0.027、0.047), respectively. There was a marked association between the low expression of SBEM group and high expression group in lymphatic metastasis (\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.042、0.039) in the Han and Miao ethnic, while the same results were not found in the Buyi people (\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.072 )(Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e,\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e,\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eClinicopathological characteristics of patients in Han ethnic\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eParameter\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNumber (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSubgroup\u003c/p\u003e\n\u003cp\u003ecut-offs\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSBEM\u0026thinsp;\u0026lt;\u0026thinsp;3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSBEM\u0026thinsp;=\u0026thinsp;3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e值\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNumber (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNumber (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eX\u0026thinsp;\u0026gt;\u0026thinsp;35\u003c/p\u003e\n\u003cp\u003eX\u0026thinsp;\u0026le;\u0026thinsp;35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e73.1\u003c/p\u003e\n\u003cp\u003e26.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57.1\u003c/p\u003e\n\u003cp\u003e42.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.614\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTNM staging\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eⅠ(1)\u003c/p\u003e\n\u003cp\u003eⅡ(2)\u003c/p\u003e\n\u003cp\u003eⅢ(3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23.1\u003c/p\u003e\n\u003cp\u003e53.8\u003c/p\u003e\n\u003cp\u003e23.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.3\u003c/p\u003e\n\u003cp\u003e42.8\u003c/p\u003e\n\u003cp\u003e42.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.075\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMutated\u003c/p\u003e\n\u003cp\u003eNo-mutated\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e45.8\u003c/p\u003e\n\u003cp\u003e44.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57.1\u003c/p\u003e\n\u003cp\u003e42.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.801\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLymph Node\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e38.5\u003c/p\u003e\n\u003cp\u003e61.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e71.4\u003c/p\u003e\n\u003cp\u003e28.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.042\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGrade\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLow (1)\u003c/p\u003e\n\u003cp\u003eMod(2)\u003c/p\u003e\n\u003cp\u003eHigh(3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e23\u003c/p\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39.1\u003c/p\u003e\n\u003cp\u003e34.8\u003c/p\u003e\n\u003cp\u003e26.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e28.6\u003c/p\u003e\n\u003cp\u003e42.8\u003c/p\u003e\n\u003cp\u003e28.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.212\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSize\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eX\u0026thinsp;\u0026gt;\u0026thinsp;20\u0026nbsp;mm\u003c/p\u003e\n\u003cp\u003eX\u0026thinsp;\u0026le;\u0026thinsp;20\u0026nbsp;mm\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53.8\u003c/p\u003e\n\u003cp\u003e46.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e57.1\u003c/p\u003e\n\u003cp\u003e42.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.872\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eKi67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eX\u0026thinsp;\u0026gt;\u0026thinsp;35\u003c/p\u003e\n\u003cp\u003eX\u0026thinsp;\u0026le;\u0026thinsp;35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42.3\u003c/p\u003e\n\u003cp\u003e57.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e83.3\u003c/p\u003e\n\u003cp\u003e16.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.034\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab3\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eClinicopathological characteristics of patients in Miao ethnic\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eParameter\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNumber (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSubgroup\u003c/p\u003e\n\u003cp\u003ecut-offs\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSBEM\u0026thinsp;\u0026lt;\u0026thinsp;3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSBEM\u0026thinsp;=\u0026thinsp;3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e值\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNumber (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNumber (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eX\u0026thinsp;\u0026gt;\u0026thinsp;35\u003c/p\u003e\n\u003cp\u003eX\u0026thinsp;\u0026le;\u0026thinsp;35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e84.6\u003c/p\u003e\n\u003cp\u003e15.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e71.4\u003c/p\u003e\n\u003cp\u003e28.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.523\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTNM staging\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eⅠ(1)\u003c/p\u003e\n\u003cp\u003eⅡ(2)\u003c/p\u003e\n\u003cp\u003eⅢ(3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e26.9\u003c/p\u003e\n\u003cp\u003e53.8\u003c/p\u003e\n\u003cp\u003e19.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e14.3\u003c/p\u003e\n\u003cp\u003e63.6\u003c/p\u003e\n\u003cp\u003e28.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.092\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e27\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMutated\u003c/p\u003e\n\u003cp\u003eNo-mutated\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e47.6\u003c/p\u003e\n\u003cp\u003e52.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50.0\u003c/p\u003e\n\u003cp\u003e50.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.901\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLymph Node\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003cp\u003e11\u003c/p\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e42.3\u003c/p\u003e\n\u003cp\u003e57.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e85.7\u003c/p\u003e\n\u003cp\u003e14.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.039\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGrade\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLow (1)\u003c/p\u003e\n\u003cp\u003eMod(2)\u003c/p\u003e\n\u003cp\u003eHigh(3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e37.5\u003c/p\u003e\n\u003cp\u003e33.3\u003c/p\u003e\n\u003cp\u003e29.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e33.3\u003c/p\u003e\n\u003cp\u003e33.3\u003c/p\u003e\n\u003cp\u003e33.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.361\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSize\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eX\u0026thinsp;\u0026gt;\u0026thinsp;20\u0026nbsp;mm\u003c/p\u003e\n\u003cp\u003eX\u0026thinsp;\u0026le;\u0026thinsp;20\u0026nbsp;mm\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003cp\u003e17\u003c/p\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e65.4\u003c/p\u003e\n\u003cp\u003e34.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63.6\u003c/p\u003e\n\u003cp\u003e36.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.849\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eKi67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e31\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eX\u0026thinsp;\u0026gt;\u0026thinsp;35\u003c/p\u003e\n\u003cp\u003eX\u0026thinsp;\u0026le;\u0026thinsp;35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e24\u003c/p\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e17\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e19.2\u003c/p\u003e\n\u003cp\u003e70.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e71.4\u003c/p\u003e\n\u003cp\u003e28.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.027\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003ctable id=\"Tab4\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eClinicopathological characteristics of patients in Buyi ethnic\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eParameter\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eNumber (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSubgroup\u003c/p\u003e\n\u003cp\u003ecut-offs\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSBEM\u0026thinsp;\u0026lt;\u0026thinsp;3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eSBEM\u0026thinsp;=\u0026thinsp;3\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003e\u003cem\u003eP\u003c/em\u003e值\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNumber (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eNumber (n)\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003e%\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eX\u0026thinsp;\u0026gt;\u0026thinsp;35\u003c/p\u003e\n\u003cp\u003eX\u0026thinsp;\u0026le;\u0026thinsp;35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003cp\u003e21\u003c/p\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e72.4\u003c/p\u003e\n\u003cp\u003e27.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63.6\u003c/p\u003e\n\u003cp\u003e36.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.806\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eTNM staging\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eⅠ(1)\u003c/p\u003e\n\u003cp\u003eⅡ(2)\u003c/p\u003e\n\u003cp\u003eⅢ(3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e24.0\u003c/p\u003e\n\u003cp\u003e48.0\u003c/p\u003e\n\u003cp\u003e32.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e12.5\u003c/p\u003e\n\u003cp\u003e37.5\u003c/p\u003e\n\u003cp\u003e50.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.101\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eP53\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eMutated\u003c/p\u003e\n\u003cp\u003eNo-mutated\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e22\u003c/p\u003e\n\u003cp\u003e13\u003c/p\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59.1\u003c/p\u003e\n\u003cp\u003e40.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63.6\u003c/p\u003e\n\u003cp\u003e36.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.678\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLymph Node\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e+\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003cp\u003e10\u003c/p\u003e\n\u003cp\u003e15\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40.0\u003c/p\u003e\n\u003cp\u003e60.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e62.5\u003c/p\u003e\n\u003cp\u003e37.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.072\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGrade\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e26\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eLow (1)\u003c/p\u003e\n\u003cp\u003eMod(2)\u003c/p\u003e\n\u003cp\u003eHigh(3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e20\u003c/p\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e40.0\u003c/p\u003e\n\u003cp\u003e35.0\u003c/p\u003e\n\u003cp\u003e25.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e6\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e50.0\u003c/p\u003e\n\u003cp\u003e33.3\u003c/p\u003e\n\u003cp\u003e16.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.201\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSize\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e33\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eX\u0026thinsp;\u0026gt;\u0026thinsp;20\u0026nbsp;mm\u003c/p\u003e\n\u003cp\u003eX\u0026thinsp;\u0026le;\u0026thinsp;20\u0026nbsp;mm\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e25\u003c/p\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003cp\u003e12\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e56.0\u003c/p\u003e\n\u003cp\u003e44.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e62.5\u003c/p\u003e\n\u003cp\u003e37.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.615\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eKi67\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e30\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eX\u0026thinsp;\u0026gt;\u0026thinsp;35\u003c/p\u003e\n\u003cp\u003eX\u0026thinsp;\u0026le;\u0026thinsp;35\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e23\u003c/p\u003e\n\u003cp\u003e9\u003c/p\u003e\n\u003cp\u003e14\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39.1\u003c/p\u003e\n\u003cp\u003e60.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e7\u003c/p\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e63.6\u003c/p\u003e\n\u003cp\u003e36.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.047\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFigure 2 \u0026nbsp;Kaplan-Meier estimates for DFS\u0026nbsp; by SBEM scores in Han, Miao and Buyi ethnic\u003c/p\u003e\n\u003cp\u003eFigure 3 Kaplan-Meier estimates for OS by SBEM scores in Han, Miao and Buyi ethnic\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eBreast cancer is pushed into first place in the United States and many other parts of world.Breast cancer alone is expected to account for 29% (226,870) of all new cancer cases among women \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e .Although incidence rate of breast cancer remains relatively stable in recent 5 years,its death rate declines by 34% because of the development of diagnosis and targeting medication\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e.The micro metastasis of breast cancer before primary treatment is considered to be one of the recurrence reasons that will directly impact the survival of patients.So,it is crucial to find specific markers to detected micro metastasis and provide useful information to guide early therapeutic methods of TNBC patients.\u003c/p\u003e\n\u003cp\u003eThe definition of tumor markers is broad.Tumor cells may express certain molecules at a different rate from that of normal cells,and these substances are released in the bloodstream or in other biologic fluids.Although various biological markers had been proposed for the detection of breast cancer cells,they were often affected by tumor differentiation,lower specificity and detection rate. But almost all the current clinical application of tumor markers can not reach ideal level in the identification of the tumor specificity and sensitivity, especially in TNBC at present.\u003c/p\u003e\n\u003cp\u003eSBEM was a tissue specific protein, a member of the MUC family, and its expression is highly specific to mammary gland tissue.High SBEM expression was found to be strongly associated with the histopathological detection of lymph node metastasis \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e .SBEM was a secreted protein and it was mainly located in cell membrane.Normal breast tissues were in general weakly or negative.SBEM could serve as a useful marker for breast micro metastasis,also as a specific targets for the treatment of breast cancer \u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e .\u003c/p\u003e\n\u003cp\u003eHowever,as the genomes of different races and nationalities have their own characteristics,it is of guiding significance to explore the genetic characteristics of different ethnics in the diagnosis and treatment of TNBC.The Buyi and Miao ethnic groups are the main components in Guizhou province in China.With different genetic backgrounds and lifestyles from those of the Han ethnic.As far as we knew the difference in the expression level of SBEM among different ethnic groups and its prognosis significance for survival have not been reported.The aim of this research was to analyze whether there is the same expression in different mammary tissues in different ethnics and the association of SBEM expression in tissue of TNBC patients with clinical- pathological features, DFS and OS, and to identify whether there is the same prediction results or the clinical meaning for SBEM in Han,Miao and Buyi ethnics.\u003c/p\u003e\n\u003cp\u003eResearchers have conducted many studies on SBEM as a tumor marker of breast cancer micro metastasis worldwide.RT-PCR and immunohistochemistry are used to detect the expression of gene and protein nowadays\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e.The research of O'Brien et al\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003ehas shown that SBEM are expressed relatively exclusively in breast tissue than non-breast tissue and are potential new markers for breast cancer\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e.Skliris GP\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003estudy showed that the SBEM expression rate was significantly higher in ER negative(22%) than in ER positive (13%) breast cancer tissue.Zhong Lei et al\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003estudy showed that SBEM expression rate was 53.3% in 60 patients with breast cancer the negative SBEM- mRNA resules were found in peripheral blood in 20 patients with mammary gland fibroma and 10 cases of healthy people. SBEM expression in TNBC tumor cells were related to TNM staging and axillary lymph node metastasis. The similar results were found by Yang Hua-wei et al\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e.This research shows that SBEM is mainly expressed in the cell membrane, the second expression in the cytoplasm, few expression in the nucleus. SBEM positive detection rate of breast cancer tissue is significantly higher than the breast benign tumor tissue and normal breast tissue. But there was no significant difference in the han, miao, buyi ethnic in breast cancer tissue, breast benign tumor tissue and normal breast tissue.\u003c/p\u003e\n\u003cp\u003eMany factors can affect the prognosis of breast cancer recurrence and death, including tumor histologic features, clinical and pathological features of primary tumor, lymph node status, tumor hormone levels,Her-2 state, complications, age, menopausal status, tumor size, tumor grade, TNM staging, Ki67 and P53, which can evaluate DFS and OS\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e. Ki67 is also a important marker of cell proliferation, and it has important significance for prognosis judgment in breast cance\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. In our study, SBEM expression in TNBC tumor cells were related to the ki67 in the Han, Miao and Buyi ethnic (\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.034、0.027、0.047), respectively. There was a marked associations between the low expression of SBEM group and high expression group in lymphatic metastasis (\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.042、0.039) in the Han and Miao ethnic, while the same results were not found in the Buyi people (\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.072)).Thus it can be seen that there is difference in different ethnic groups between SBEM different expression levels and metastatic tumor recurrence and the prognosis.\u003c/p\u003e\n\u003cp\u003eThe past studies have shown that SBEM correlated with the prognosis of patients.\u003c/p\u003e\n\u003cp\u003eBreast cancer stem cell scan obtain higher resistance and high invasive due to their high plasticity\u003csup\u003e[\u003cspan class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. The previous studies have not been reported whether there is the same prediction results or the clinical meaning for the same tumor marker in different ethnics.The experiment has carried on the preliminary exploration to this. In our study, we found that DFS and OS function curves showed the large separation between the high expression group and low expression group. There was significant difference in DFS ( \u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.028、0.013)and OS ( \u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.09、0.037)between the high expression group and low expression group in the Han and Miao ethnic.But there was no significant difference in DFS (\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.053 ) and OS (\u003cspan class=\"BoldItalic\"\u003eP\u003c/span\u003e\u0026thinsp;=\u0026thinsp;0.088 )in the Buyi people.Thus it can be seen there is different prognostic significance in different ethnic groups for SBEM different expression levels.\u003c/p\u003e\n\u003cp\u003eIn conclusion, this research shows that SBEM positive detection rate was no significant difference in the han, miao and buyi ethnic in breast cancer tissue, breast benign tumor tissue and normal breast tissue.The SBEM expression level is related to the prognosis of TNBC patients and its clinical significance is not exactly the same in different ethnics ,which can provide a more reasonable choice for clinical individualized treatment and prognostic judgement and reduce a certain amount of medical costs. However, it needs more centers to participate in further study because this is just a retrospective single-center study and the small sample size limits to some extent the generalization of the findings made in the study.\u003c/p\u003e"},{"header":"Conclusion","content":" \u003cp\u003eWe have demonstrated that the SBEM positive detection rate was no significant difference in the han, miao and buyi ethnic groups in breast cancer tissue, breast benign tumor tissue and normal breast tissue.The expression of SBEM does significantly correlate with a DFS and an OS of TNBC patients in the han, miao and buyi ethnic. But it is not obvious for prognostic significance in Buyi ethnic.The distinction in different ethnic groups shall certainly provide a more reasonable choice for clinical individualized treatment and prognostic judgement in TNBC patients.\u003c/p\u003e "},{"header":"Abbreviations","content":"SBEM: Small breast epithelial mucin; TNBC: Triple-negative breast cancer;DFS: Disease-free survival; OS: Overall survival; ER: Estrogen receptor; PR: Progesterone receptor; HER2: Human epidermal growth factor receptor-2; TNM: Tumor node metastasis; IHC: immunohistochemical; PB: Peripheral blood; RT–PCR: Reverse transcription polymerase chain reaction; FISH: Fluorescence in situhybridization; NCCN: National comprehensive cancer network; CEA: Carcinoembryonic antigen."},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConsent \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\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\u003eLL contributed to the study design, data acquisition and analysis and drafted the manuscript; WL was involved in data acquisition and revision of the manuscript; QL and YY worked on aspects of data acquisition and analysis; HY contributed to the study design and data-analysis, developed the algorithm and coordinated the study; LH conceived and coordinated the study. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Dr. Xie Xiaodogn and Dr. Jing Peng for expert technical assistance with IHC. We thank Dr. Yang Jie, Dr. Liu Hui and Dr. You Hui for secretarial and organizational support in our experiments. We also thank Dr. Liu Hongshuo and Dr. Wang Xu for critical revision of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDepartment of Oncology, Third Affiliated Hospital of Guizhou Medical University\u003c/p\u003e"},{"header":"References","content":"\u003cp\u003e[1] Siegel R L, Miller K D,Jemal A.Cancer statistics,2020［J］.CA Cancer J Clin,2020,70(1):7-30.\u003c/p\u003e\n\u003cp\u003e[2] Ahmedin J，Rebecca S，Elizabeth W，\u003cem\u003eet a1\u003c/em\u003e．Cancer statistics 2007[J]．CA Cancer J Clin，2007，57：43-66．\u003c/p\u003e\n\u003cp\u003e[3] Jemal A, Siegel R, Xu J, e\u003cem\u003et al.\u003c/em\u003e. Cancer statistics,2010.CA Cancer J Clin 2010; 60: 277-300.\u003c/p\u003e\n\u003cp\u003e[4] Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomized trials. 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The clinical significance of\u0026nbsp;the peripheral blood expression of SBEM - mRNA and CEA in breast cancer patients.Chinese journal of clinical oncology, 2008,35(23): 1344-1347.\u003c/p\u003e\n\u003cp\u003e[25] Yang HW, Cao J, Yang NW,\u003cem\u003e et, al\u003c/em\u003e\u003cem\u003e. \u003c/em\u003eExpression of small breast epithelial mucin mRNA\u0026nbsp;in peripheral blood of breast cancer patients and its clinical significance. Ai Zheng. 2005, 24(7), 842-845.\u003c/p\u003e\n\u003cp\u003e[26] Ravdin PM, Siminoff LA,\u003cem\u003e et al\u003c/em\u003e\u003cem\u003e.\u003c/em\u003e Computer program to assist in making decision about adjuvant therapy for women with early breast cancer. J Clin Oncol 2001, 19: 980-991.\u003c/p\u003e\n\u003cp\u003e[27] Olivotto IA, Bajdik CD, Ravdin PM, e\u003cem\u003et al. \u003c/em\u003ePopulation-Based Validation of thePrognostic Model Adjuvant for early breast cancer. J Clin Oncol 2005, 23: 2716-2725.\u003c/p\u003e\n\u003cp\u003e[28] Weigel MT, Dowsett M. Current and emerging biomarkers in breast cancer: prognosis and prediction. Endocrine-Related Cancer 2010, 17: R245-262.\u003c/p\u003e\n\u003cp\u003e[29] Lindstrom L S,Yau, C,Czene K,et al.Intratumor heterogeneity of the estrogen\u0026nbsp;eceptor and the long-term risk of fatal breast cancer［J］.J Natl Cancer Inst,\u0026nbsp;2018,110(7):726-733.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"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},"keywords":"small breast epithelial mucin; breast cancer; DFS; OS; ethnic difference","lastPublishedDoi":"10.21203/rs.3.rs-56422/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-56422/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e To investigate \u0026nbsp;Small breast epithelial mucin(SBEM) expression difference in\u0026nbsp;mammary tissues and relationship with survival in thetriple-negative\u0026nbsp;breast cancer(TNBC) patients in Han, Buyi and Miao ethnic.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: In our study, SBEM protein expressions were detected by means of immunohistochemistry in 297 patients diagnosed from 2014 to 2015,including 99 normal breast tissue specimens, 99 cases of breast benign tumor tissue specimens and 99\u0026nbsp;tissues specimens from TNBC patients.Each set of tissue specimens contains 33 samples from Han,Miao and Buyi ethnics, respectively.We analyze the expression of SBEM in different mammary\u0026nbsp;tissues in different ethnics and the association of different SBEM expression levels in tissue of TNBC patients with clinical- pathological features, DFS and OS in Han,Miao and Buyi ethnics,respectively. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e SBEM expression in breast cancer tumor cells were related to the ki67 in the Han, Miao and Buyi ethnic (\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e=0.034、0.027、0.047), respectively. There was a marked associations between the SBEM expression level and lymphatic\u0026nbsp;metastasis\u0026nbsp;(\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e \u003c/strong\u003e= 0.042、0.039) in the Han and Miao ethnic, while the\u0026nbsp;same\u0026nbsp;results were not found in the Buyi people (\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e=0.072).There was significant difference in DFS ( \u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e =0.028、0.013)and OS ( \u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e =0.09、0.037) between the high expression group and low expression group in the Han and Miao ethnic.But there was no significant difference in DFS (\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e = 0.053 ) and OS (\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e = 0.088 )in the Buyi people.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThe SBEM positive detection rate was no significant difference in the han, miao and buyi ethnic groups. SBEM was associated with DFS and OS in the Han and Miao ethnic, while no correlation in the Buyi ethnic.\u003c/p\u003e","manuscriptTitle":"Study on\u0026nbsp;the small breast epithelial mucin tumor tissue expression difference\u0026nbsp;and\u0026nbsp;its relationship with survival in\u0026nbsp;triple-negative\u0026nbsp;breast cancer\u0026nbsp;patients in\u0026nbsp;Han, Miao and Buyi ethnic","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-08-11 17:59:14","doi":"10.21203/rs.3.rs-56422/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":"6e53f90f-f398-4d87-88d9-ae18e443c8d4","owner":[],"postedDate":"August 11th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":275073,"name":"Pathology"}],"tags":[],"updatedAt":"2020-10-20T22:15:47+00:00","versionOfRecord":[],"versionCreatedAt":"2020-08-11 17:59:14","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-56422","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-56422","identity":"rs-56422","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}