本文選題：絲氨酸蛋白酶4 + 胃癌�。� 參考：《安徽醫(yī)科大學》2017年碩士論文

【摘要】：背景與目的:胃癌是一種高度惡性的疾病,并被認為是由遺傳、表觀遺傳和環(huán)境影響等多種因素引起的,其低診斷率、低手術(shù)切除率是胃癌患者預后不良的主要原因。許多已被開發(fā)的用于判斷,治療和及判定預后生物學標志物,例如血清癌胚抗原(CEA)和胃癌組織HER2表達已被建議作為胃癌標志物并用于臨床實踐。然而,它們的低靈敏度和低特異性限制了其應(yīng)用。診斷標志物,預后指標及有效的治療靶點的缺乏仍然是胃癌臨床診療以及預后效果不佳主要因素。因此,繼續(xù)深入對GC的發(fā)病機制研究,以便發(fā)現(xiàn)和開發(fā)針對胃癌的新型的診斷和預后的分子標志物,對于提高胃癌患者生活和生存質(zhì)量是目前亟需解決的問題。探索跨膜絲氨酸蛋白酶4(Transmembrane protease,serine 4 TMPRSS 4)在胃惡性腫瘤中表達水平及其與GC患者臨床病理學特征的相互關(guān)系,分析TMPRSS 4蛋白表達水平與GC患者預后生存的影響,以期尋找GC新型的生物學標志物。方法:1.收集2014.7-2015.2間41例在安徽省立醫(yī)院明確診斷為GC(術(shù)前胃鏡及病理活檢或術(shù)后病理確診)并接受標準胃癌切除術(shù)(D2)的患者的新鮮組織標本,留取一定量癌變組織及癌旁胃粘膜(癌旁組織定義:距癌腫"g5 cm的正常胃粘膜組織),裝入已編號的滅菌凍存管,迅速轉(zhuǎn)移放入安徽省立醫(yī)院普外科實驗室-80℃深低溫冰柜中儲存,運用RT-qPCR方法檢測TMPRSS 4 mRNA在胃癌及癌旁組織中的表達豐度。2.選取2010.7.1到2012.7.1之間在安徽省立醫(yī)院明確診斷為GC并接受胃惡性腫瘤根治性切除術(shù)的患者115例,所有標本在手術(shù)切除半小時內(nèi)及時放入固定液中(4%甲醛)、留取一定量癌變組織及癌旁組織,進行免疫組化實驗,檢測TMPRSS 4在癌組織及癌旁組織中的的表達水平;分析其表達與GC患者年齡、性別、腫瘤大小、胃癌組織分化程度、淋巴結(jié)轉(zhuǎn)移數(shù)、及腫瘤TNM分期等臨床病理學特征的關(guān)系。3.通過電話及門診隨訪獲取“2”中115例胃癌患者的臨床預后信息例如腫瘤復發(fā)、患者死亡等患者相關(guān)預后資料,使用Kaplan-Meier曲線分析TMPRSS 4蛋白的異常表達與胃癌患者總生存期(Overall survival OS)的相互關(guān)系,運用單因素分析方法及Cox回歸多因素分析模型明確患者年齡、性別、腫瘤大小、胃癌組織分化程度、淋巴結(jié)轉(zhuǎn)移數(shù)、及腫瘤TNM分期等臨床病理學特征與胃癌患者TMPRSS 4蛋白表達豐度等變量間的相關(guān)性。結(jié)果1.RT-qPCR結(jié)果提示TMPRSS4 mRNA在GC患者癌變部位表達量顯著高于其匹配癌旁組織中的表達水平,差異有統(tǒng)計學意義0.86±0.31vs0.41±0.15,P0.05)。2.免疫組化結(jié)果顯示:TMPRSS4在胃癌組織中陽性表達是70.4%(81/115),顯著高于其在良性組織中的陽性表達率19.5%(9/41),差異有統(tǒng)計學意義(P0.001).3.臨床資料分析:高表達TMPRSS4與胃腫瘤的分化程度、轉(zhuǎn)移淋巴結(jié)數(shù)及臨床分期(TNM法)顯著相關(guān)(均P0.001),而與患者年齡、性別、腫瘤大小等無明顯相關(guān)。4.TMPRSS4是GC患者OS及DFS獨立影響因素,能在一定程度上預測GC患者預后情況。結(jié)論:TMPRSS 4在胃癌組織中的高表達與胃癌患者的分化程度低、轉(zhuǎn)移淋巴結(jié)數(shù)多,及較高的臨床分期等相關(guān)臨床病理特征密切相關(guān),TMPRSS 4有可能作為一個新型的的胃癌的生物標志物,有可能預測GC患者的預后。
[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.
【學位授予單位】：安徽醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R735.2

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