PD-L1在胃癌组织中的表达及其临床意义

发布时间：2018-04-15 03:01

  本文选题：胃癌 + 程序性死亡配体1　； 参考：《江苏大学》2017年硕士论文

【摘要】：研究背景:胃癌是我国最常见的致命性肿瘤之一,5年生存率仅为20%至25%。虽然近年来诊断技术不断提高,但是大部患者在发现胃癌时已有明显的转移征象,不仅需要手术治疗,还需要结合围手术期化疗/放疗予以辅助,甚至部分晚期胃癌患者在发现时已出现远处转移,失去了手术治疗的机会。因此,传统手术结合化放疗方法治疗胃癌预后往往不尽如人意,尤其是对于那些化疗无效或耐受很差的患者。免疫疗法是21世纪以来快速发展的新兴疗法,它以其在中晚期肿瘤中的显著疗效得到国内外学者的广泛关注,其中寻找抗体作用的有效靶点是免疫疗法在癌症治疗中的关键所在。程序性死亡-配体1(programmed cell death-ligand 1,PD-L1)作为B7/CD28家族的成员,在T细胞上与其受体程序性死亡受体-1(programmed cell death 1,PD-1)结合对细胞因子的分泌和T细胞增殖起负调节作用[1],从而帮助肿瘤细胞逃避免疫杀伤。已发现PD-L1表达于多种恶性肿瘤中,且已证实PD-L1高表达于非小细胞肺癌、肾细胞癌和食道癌并与患者临床病理特征密切相关[2-4]。该研究通过比较PD-L1在胃癌组织及癌旁组织中的表达,并与一系列的临床病理特征做相关性分析,探讨其在胃癌发生、发展中的作用。研究目的:通过探究程序性死亡-配体1(programmed death ligand 1,PD-L1)在胃癌组织及癌旁组织中的表达情况,并与一些列临床病理资料做相关性分析,挖掘其临床价值,讨论其在胃癌发生、发展中的作用,以期能为胃癌的早期诊断,监测转移,和预后提供理论依据。研究方法:(1)标本收集:收集胃癌患者癌及癌旁组织及患者临床病理资料(年龄、性别、肿瘤大小、浸润深度等)(2)免疫组化实验:通过免疫组织化学实验对胃癌患者癌及癌旁组织上的PD-L1的表达做半定量研究。(3)Wilcoxon秩和检验:分析胃癌患者癌组织与癌旁组织中PD-L1的表达差异。(4)χ~2检验:分析胃癌患者PD-L1的表达与临床病理特征之间的相关性。研究结果:(1)PD-L1在胃癌组织中的表达明显高于癌旁组织(Z=3.104,P=0.002)。(2)PD-L1的表达与胃癌分化程度(χ~2=8.740,P=0.013)及浸润深度(χ~2=8.960,P=0.030)有关,Ⅲ期、Ⅳ期患者PD-L1的表达明显高于Ⅰ期、Ⅱ期患者(χ~2=4.133,P=0.042)。结论:(1)PD-L1在胃癌组织中高表达,提示其可能参与胃癌的形成,并可能在胃癌的发生发展中起重要作用。(2)分化程度和浸润深度不同的胃癌患者,其PD-L1阳性表达率有差异,这表明PD-L1可能是反映胃癌分化和侵袭的生物学指标,这也为PD-L1成为肿瘤免疫治疗靶点提供了可能。
[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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