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PD-L1在胃癌組織中的表達及其臨床意義

發(fā)布時間:2018-04-15 03:01

  本文選題:胃癌 + 程序性死亡配體1; 參考:《江蘇大學》2017年碩士論文


【摘要】:研究背景:胃癌是我國最常見的致命性腫瘤之一,5年生存率僅為20%至25%。雖然近年來診斷技術不斷提高,但是大部患者在發(fā)現胃癌時已有明顯的轉移征象,不僅需要手術治療,還需要結合圍手術期化療/放療予以輔助,甚至部分晚期胃癌患者在發(fā)現時已出現遠處轉移,失去了手術治療的機會。因此,傳統(tǒng)手術結合化放療方法治療胃癌預后往往不盡如人意,尤其是對于那些化療無效或耐受很差的患者。免疫療法是21世紀以來快速發(fā)展的新興療法,它以其在中晚期腫瘤中的顯著療效得到國內外學者的廣泛關注,其中尋找抗體作用的有效靶點是免疫療法在癌癥治療中的關鍵所在。程序性死亡-配體1(programmed cell death-ligand 1,PD-L1)作為B7/CD28家族的成員,在T細胞上與其受體程序性死亡受體-1(programmed cell death 1,PD-1)結合對細胞因子的分泌和T細胞增殖起負調節(jié)作用[1],從而幫助腫瘤細胞逃避免疫殺傷。已發(fā)現PD-L1表達于多種惡性腫瘤中,且已證實PD-L1高表達于非小細胞肺癌、腎細胞癌和食道癌并與患者臨床病理特征密切相關[2-4]。該研究通過比較PD-L1在胃癌組織及癌旁組織中的表達,并與一系列的臨床病理特征做相關性分析,探討其在胃癌發(fā)生、發(fā)展中的作用。研究目的:通過探究程序性死亡-配體1(programmed death ligand 1,PD-L1)在胃癌組織及癌旁組織中的表達情況,并與一些列臨床病理資料做相關性分析,挖掘其臨床價值,討論其在胃癌發(fā)生、發(fā)展中的作用,以期能為胃癌的早期診斷,監(jiān)測轉移,和預后提供理論依據。研究方法:(1)標本收集:收集胃癌患者癌及癌旁組織及患者臨床病理資料(年齡、性別、腫瘤大小、浸潤深度等)(2)免疫組化實驗:通過免疫組織化學實驗對胃癌患者癌及癌旁組織上的PD-L1的表達做半定量研究。(3)Wilcoxon秩和檢驗:分析胃癌患者癌組織與癌旁組織中PD-L1的表達差異。(4)χ~2檢驗:分析胃癌患者PD-L1的表達與臨床病理特征之間的相關性。研究結果:(1)PD-L1在胃癌組織中的表達明顯高于癌旁組織(Z=3.104,P=0.002)。(2)PD-L1的表達與胃癌分化程度(χ~2=8.740,P=0.013)及浸潤深度(χ~2=8.960,P=0.030)有關,Ⅲ期、Ⅳ期患者PD-L1的表達明顯高于Ⅰ期、Ⅱ期患者(χ~2=4.133,P=0.042)。結論:(1)PD-L1在胃癌組織中高表達,提示其可能參與胃癌的形成,并可能在胃癌的發(fā)生發(fā)展中起重要作用。(2)分化程度和浸潤深度不同的胃癌患者,其PD-L1陽性表達率有差異,這表明PD-L1可能是反映胃癌分化和侵襲的生物學指標,這也為PD-L1成為腫瘤免疫治療靶點提供了可能。
[Abstract]:Background: gastric cancer is one of the most common fatal tumors in China. The 5-year survival rate is only 20% to 25%.Although diagnostic techniques have been improved in recent years, most patients have obvious metastatic signs when they find gastric cancer. They need not only surgical treatment, but also perioperative chemotherapy / radiotherapy to assist them.Even some patients with advanced gastric cancer had distant metastasis at the time of discovery and lost the opportunity of surgical treatment.Therefore, the prognosis of gastric cancer treated by conventional surgery combined with chemoradiotherapy is often unsatisfactory, especially for those patients whose chemotherapy is ineffective or poorly tolerated.Immunotherapy is a rapidly developing new therapy in the 21st century. It has attracted wide attention from scholars at home and abroad for its remarkable efficacy in advanced tumors.The key of immunotherapy in cancer treatment is to find the effective target of antibody.The ligand 1(programmed cell death-ligand 1 PD-L1 is a member of the B7/CD28 family.Binding to its receptor programmed cell death 1PD-1 on T cells can negatively regulate cytokine secretion and T cell proliferation, thus helping tumor cells escape from immune killing.It has been found that PD-L1 is expressed in various malignant tumors, and it has been confirmed that PD-L1 is highly expressed in non-small cell lung cancer, renal cell carcinoma and esophageal carcinoma and is closely related to the clinicopathological features of the patients [2-4].In this study, we compared the expression of PD-L1 in gastric cancer tissues and adjacent tissues, and analyzed the correlation with a series of clinicopathological features to explore the role of PD-L1 in the carcinogenesis and development of gastric cancer.Objective: to explore the expression of 1(programmed death ligand 1 PD-L1) in gastric carcinoma and its adjacent tissues, and to analyze the correlation with some clinicopathological data, so as to explore its clinical value and discuss its occurrence in gastric cancer.The role of development can provide theoretical basis for early diagnosis, monitoring metastasis and prognosis of gastric cancer.Methods: to collect the clinicopathological data (age, sex, tumor size) of patients with gastric cancer and their adjacent tissues, and the clinicopathological data (age, sex, tumor size).Immunohistochemical study on the expression of PD-L1 in carcinoma and adjacent tissues of patients with gastric carcinoma by immunohistochemical method. Wilcoxon rank sum test: analysis of the surface of PD-L1 in cancer and paracancerous tissues of gastric cancer patients蠂 2 test: the correlation between the expression of PD-L1 and clinicopathological features in patients with gastric cancer was analyzed.Results the expression of PD-L1 in gastric cancer tissues was significantly higher than that in adjacent tissues of gastric cancer. The expression of PD-L1 was related to the degree of differentiation (蠂 ~ (2) 2) and the depth of invasion (蠂 ~ (2)). The expression of PD-L1 in stage 鈪,

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