跨膜丝氨酸蛋白酶4在胃癌组织中表达及其临床意义

发布时间：2018-07-06 18:44

本文选题：丝氨酸蛋白酶4 + 胃癌　；参考：《安徽医科大学》2017年硕士论文

【摘要】：背景与目的:胃癌是一种高度恶性的疾病,并被认为是由遗传、表观遗传和环境影响等多种因素引起的,其低诊断率、低手术切除率是胃癌患者预后不良的主要原因。许多已被开发的用于判断,治疗和及判定预后生物学标志物,例如血清癌胚抗原(CEA)和胃癌组织HER2表达已被建议作为胃癌标志物并用于临床实践。然而,它们的低灵敏度和低特异性限制了其应用。诊断标志物,预后指标及有效的治疗靶点的缺乏仍然是胃癌临床诊疗以及预后效果不佳主要因素。因此,继续深入对GC的发病机制研究,以便发现和开发针对胃癌的新型的诊断和预后的分子标志物,对于提高胃癌患者生活和生存质量是目前亟需解决的问题。探索跨膜丝氨酸蛋白酶4(Transmembrane protease,serine 4 TMPRSS 4)在胃恶性肿瘤中表达水平及其与GC患者临床病理学特征的相互关系,分析TMPRSS 4蛋白表达水平与GC患者预后生存的影响,以期寻找GC新型的生物学标志物。方法:1.收集2014.7-2015.2间41例在安徽省立医院明确诊断为GC(术前胃镜及病理活检或术后病理确诊)并接受标准胃癌切除术(D2)的患者的新鲜组织标本,留取一定量癌变组织及癌旁胃粘膜(癌旁组织定义:距癌肿"g5 cm的正常胃粘膜组织),装入已编号的灭菌冻存管,迅速转移放入安徽省立医院普外科实验室-80℃深低温冰柜中储存,运用RT-qPCR方法检测TMPRSS 4 mRNA在胃癌及癌旁组织中的表达丰度。2.选取2010.7.1到2012.7.1之间在安徽省立医院明确诊断为GC并接受胃恶性肿瘤根治性切除术的患者115例,所有标本在手术切除半小时内及时放入固定液中(4%甲醛)、留取一定量癌变组织及癌旁组织,进行免疫组化实验,检测TMPRSS 4在癌组织及癌旁组织中的的表达水平;分析其表达与GC患者年龄、性别、肿瘤大小、胃癌组织分化程度、淋巴结转移数、及肿瘤TNM分期等临床病理学特征的关系。3.通过电话及门诊随访获取“2”中115例胃癌患者的临床预后信息例如肿瘤复发、患者死亡等患者相关预后资料,使用Kaplan-Meier曲线分析TMPRSS 4蛋白的异常表达与胃癌患者总生存期(Overall survival OS)的相互关系,运用单因素分析方法及Cox回归多因素分析模型明确患者年龄、性别、肿瘤大小、胃癌组织分化程度、淋巴结转移数、及肿瘤TNM分期等临床病理学特征与胃癌患者TMPRSS 4蛋白表达丰度等变量间的相关性。结果1.RT-qPCR结果提示TMPRSS4 mRNA在GC患者癌变部位表达量显著高于其匹配癌旁组织中的表达水平,差异有统计学意义0.86±0.31vs0.41±0.15,P0.05)。2.免疫组化结果显示:TMPRSS4在胃癌组织中阳性表达是70.4%(81/115),显著高于其在良性组织中的阳性表达率19.5%(9/41),差异有统计学意义(P0.001).3.临床资料分析:高表达TMPRSS4与胃肿瘤的分化程度、转移淋巴结数及临床分期(TNM法)显著相关(均P0.001),而与患者年龄、性别、肿瘤大小等无明显相关。4.TMPRSS4是GC患者OS及DFS独立影响因素,能在一定程度上预测GC患者预后情况。结论:TMPRSS 4在胃癌组织中的高表达与胃癌患者的分化程度低、转移淋巴结数多,及较高的临床分期等相关临床病理特征密切相关,TMPRSS 4有可能作为一个新型的的胃癌的生物标志物,有可能预测GC患者的预后。
[Abstract]:Background and purpose: gastric cancer is a highly malignant disease and is considered to be caused by a variety of factors such as heredity, epigenetic and environmental effects. Low diagnostic rates and low surgical excision rates are the main causes of poor prognosis in gastric cancer. Many developed methods have been used to judge, treat and determine prognostic biomarkers, such as serum cancer. HER2 expression of embryonic antigen (CEA) and gastric cancer tissue has been suggested as a marker for gastric cancer and used in clinical practice. However, their low sensitivity and low specificity limit its application. Diagnostic markers, prognostic indicators and the lack of effective therapeutic targets are still the main factors for the clinical diagnosis and treatment of gastric cancer and poor prognosis. The study of the pathogenesis of GC, in order to discover and develop new molecular markers for diagnosis and prognosis of gastric cancer, is an urgent problem to improve the life and quality of life of gastric cancer patients. To explore the expression level of transmembrane serine protease 4 (Transmembrane protease, serine 4 TMPRSS 4) and its expression in gastric cancer. The relationship between the clinicopathological features of GC patients and the influence of the TMPRSS 4 protein expression level and the prognosis of GC patients were analyzed in order to find a new biological marker of GC. Methods: 1., 41 cases of 2014.7-2015.2 were collected and diagnosed as GC (preoperative gastroscopy and pathological biopsy or postoperative pathological diagnosis) and accepted standard stomach. The fresh tissue specimens of the patients with cancer resection (D2) were left with a certain amount of cancerous tissue and paracancerous gastric mucosa (defined by the paracancerous tissue: normal gastric mucosa of G5 cm from cancer), loaded into the numbered sterilized cryopreservation tube, and the rapid metastasis was stored in the Department of general surgery of the Department of general surgery, Anhui Provincial Hospital, the cryogenic cryogenic refrigerator, and the RT-qPCR method was used for the detection of TM. Expression abundance of PRSS 4 mRNA in gastric and paracancerous tissues:.2. selected from 2010.7.1 to 2012.7.1 in Anhui Provincial Hospital, which were clearly diagnosed as GC and received radical resection of gastric malignant tumors. All specimens were placed in a fixed solution (4% formaldehyde) within half an hour of surgical excision, leaving a certain amount of cancerous tissue and para cancerous tissue. The expression level of TMPRSS 4 in cancer tissue and para cancerous tissue was detected by immunohistochemistry. The relationship between the expression of TMPRSS and the clinicopathological features of GC patients' age, sex, tumor size, degree of differentiation of gastric carcinoma, lymph node metastasis, and tumor TNM staging, and.3. were followed up by telephone and outpatient follow-up to obtain 115 cases of gastric cancer in "2" The clinical prognostic information, such as tumor recurrence, patient mortality and other patients' related prognostic data, was used to analyze the relationship between the abnormal expression of TMPRSS 4 protein and the total survival time (Overall survival OS) of gastric cancer patients with the Kaplan-Meier curve. The patient's age, sex, and tumor were determined by the single factor analysis and the Cox regression multivariate analysis model. The correlation between the size, the degree of differentiation, the number of lymph nodes, the number of lymph nodes, and the TNM staging of the tumor and the expression of the expression of TMPRSS 4 protein in the patients with gastric cancer. Results 1.RT-qPCR results showed that the expression of TMPRSS4 mRNA in the cancerous sites of GC patients was significantly higher than that of the paracancerous tissue in the matched tissues, and the difference was statistically significant. The immunohistochemical results of 0.86 + 0.31vs0.41 + 0.15, P0.05).2. showed that the positive expression of TMPRSS4 in gastric carcinoma was 70.4% (81/115), significantly higher than the positive expression rate of 19.5% (9/41) in the benign tissues (9/41). The difference was statistically significant (P0.001) the clinical data of.3.: high expression of TMPRSS4 and the degree of differentiation of gastric tumor and the number of metastatic lymph nodes And the clinical staging (TNM) was significantly correlated (P0.001), and there was no significant correlation with age, sex, and tumor size of the patients..4.TMPRSS4 was the independent factor of OS and DFS in GC patients. It can predict the prognosis of GC patients to a certain extent. Conclusion: the high expression of TMPRSS 4 in gastric cancer tissues is lower than the degree of differentiation of gastric cancer patients, and the number of metastatic lymph nodes is much more. TMPRSS 4 is likely to be a new biomarker for gastric cancer and may predict the prognosis of GC patients.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.2

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