PD-L1和PD-1在胃癌组织中的表达及其临床意义

发布时间：2018-01-19 14:12

本文关键词： 胃肿瘤肿瘤免疫 PD-L1 PD-1 预后　出处：《安徽医科大学》2015年硕士论文　论文类型：学位论文

【摘要】：目的:检测PD-L1和PD-1在胃癌组织中的表达情况,探讨其与患者临床病理特征和预后生存的关系。方法:收集安徽医科大学第一附属医院2007~2009年期间218例行胃癌根治术患者的肿瘤石蜡组织标本及其对应的临床病例资料,有淋巴结转移的113例收集其转移淋巴结标本,并随机选取其中20例距肿瘤组织5 cm的癌旁组织作为对照组。采用免疫组织化学PV-6000两步法检测其中PD-L1和PD-1蛋白表达,采用染色强度分级和阳性细胞密度分级的乘积评定PD-L1表达,采用细胞计数法评估PD-1表达,采用SPSS17.0统计软件分析其与患者各项临床指标及预后的关系。结果:1.胃癌组织中PD-L1蛋白表达阳性率为66.97%,主要定位在胃癌细胞和癌间质淋巴细胞的细胞质和细胞膜,其中癌细胞上表达阳性率为66.05%,癌间质淋巴细胞上表达阳性率为33.94%;PD-1蛋白表达阳性率为40.83%,主要定位在肿瘤浸润淋巴细胞(TIL)的细胞质和细胞膜;20例癌旁组织均无PD-L1和PD-1蛋白表达。转移淋巴结中PD-L1和PD-1蛋白有表达,并且与其对应的原发肿瘤组织表达高度一致,一致率分别为76.1%和86.7%。2.胃癌组织中癌间质浸润的淋巴细胞上PD-L1表达与PD-1表达呈显著正相关(P=0.006),而癌细胞上PD-L1表达与PD-1表达无显著相关性(P0.05)。3.胃癌细胞中PD-L1表达与p TNM分期(P0.01)、浸润层面(P0.01)、淋巴结转移情况(P0.01)及脉管癌栓(P0.05)密切相关,而胃癌间质细胞中PD-L1表达仅与淋巴结转移与否(P0.05)相关。胃癌组织中PD-1表达与各临床病理特征均无显著相关性。4.单因素COX回归分析显示,p TNM分期较晚、肿瘤大小较大、淋巴结转移阳性及胃癌细胞上PD-L1过表达是影响预后的不良因素。多因素COX回归分析显示,p TNM分期、肿瘤大小、淋巴结转移和癌细胞PD-L1表达是预后的独立因素。Kaplan-Meier生存曲线分析显示胃癌细胞及癌间质中PD-L1表达与患者术后生存期均呈现显著相关,PD-L1阳性表达者较阴性者术后生存期短,log-rank检验生存率差异有统计学意义(P0.01)。胃癌组织中PD-1阳性表达与否与术后生存期无关。结论:1.胃癌组织中PD-L1和PD-1均有表达,并明显高于癌旁组织,且癌间质PD-L1表达与TIL中PD-1表达呈显著正相关,而癌细胞上PD-L1表达与PD-1表达无显著相关性。2.胃癌转移淋巴结中PD-L1和PD-1均有表达,与其原发部位的表达情况具有高度一致性。3.胃癌细胞中PD-L1表达与多项临床病理特征密切相关,而胃癌间质细胞中PD-L1表达仅与淋巴结转移与否相关。胃癌组织中PD-1表达与各临床病理特征均无显著相关性。4.PD-L1阳性表达的胃癌患者较阴性者术后生存期短,提示PD-L1表达是影响预后的独立因素。
[Abstract]:Objective: to detect the expression of PD-L1 and PD-1 in gastric carcinoma. Methods: to explore the relationship between the clinicopathological features and prognosis of the patients. The paraffin tissue specimens of 218 patients undergoing radical gastrectomy for gastric cancer and their clinical data were collected from the first affiliated Hospital of Anhui Medical University from 2007 to 2009. Lymph node specimens were collected from 113 patients with lymph node metastasis. The expression of PD-L1 and PD-1 protein was detected by immunohistochemical PV-6000 two-step method in 20 cases of paracancerous tissues 5 cm away from the tumor tissue as control group. The expression of PD-L1 was evaluated by the product of staining intensity grade and positive cell density grade, and the expression of PD-1 was evaluated by cell count method. SPSS17.0 software was used to analyze the relationship between the expression of PD-L1 protein and the clinical indexes and prognosis. Results the positive rate of PD-L1 protein expression in gastric cancer was 66.97%. It was mainly located in the cytoplasm and cell membrane of gastric cancer cells and stromal lymphocytes. The positive expression rate of cancer cells was 66.05, and the positive rate of cancer interstitial lymphocytes was 33.94. The positive rate of PD-1 protein expression was 40.83%, mainly located in the cytoplasm and cell membrane of tumor infiltrating lymphocytes. There was no PD-L1 and PD-1 protein expression in 20 paracancerous tissues, but PD-L1 and PD-1 proteins were expressed in metastatic lymph nodes, which were highly consistent with the corresponding primary tumor tissues. The consistent rates were 76.1% and 86.7 / 0.2.The expression of PD-L1 was positively correlated with the expression of PD-1 in the lymphocytes of interstitial infiltration of gastric cancer. However, there was no significant correlation between the expression of PD-L1 and the expression of PD-1 in gastric cancer cells. The expression of PD-L1 in gastric cancer cells was significantly correlated with that of p TNM staging (P0.01). P0.01, lymph node metastasis (P0.01) and vascular tumor embolus (P0.05) were closely related. The expression of PD-L1 in stromal cells of gastric cancer was only correlated with lymph node metastasis (P0.05). There was no significant correlation between the expression of PD-1 and the clinicopathological characteristics of gastric cancer. 4. Univariate COX regression analysis showed. P TNM staging, large tumor size, positive lymph node metastasis and overexpression of PD-L1 on gastric cancer cells were the adverse factors affecting the prognosis. Multivariate COX regression analysis showed that p TNM staging. Tumor size. Lymph node metastasis and PD-L1 expression were independent prognostic factors. Kaplan-Meier survival curve analysis showed that the expression of PD-L1 in gastric cancer cells and stroma was significantly correlated with postoperative survival. There was a significant correlation. The survival time of patients with positive expression of PD-L1 was shorter than that of patients with negative expression. The difference of survival rate in log-rank test was statistically significant (P 0.01). The positive expression of PD-1 in gastric cancer was not related to the survival time after operation. Conclusion 1. Both PD-L1 and PD-1 were expressed in gastric carcinoma. The expression of PD-L1 in stromal tissue was significantly higher than that in paracancerous tissue, and there was a significant positive correlation between the expression of PD-L1 and PD-1 in TIL. However, there was no significant correlation between PD-L1 expression and PD-1 expression in cancer cells. 2. Both PD-L1 and PD-1 were expressed in metastatic lymph nodes of gastric cancer. The expression of PD-L1 in gastric cancer cells is closely related to many clinicopathological features. However, the expression of PD-L1 in the interstitial cells of gastric cancer was only related to lymph node metastasis. There was no significant correlation between the expression of PD-1 and the clinicopathological characteristics of gastric cancer. 4. The positive expression of PD-L1 in gastric cancer patients. The survival time was shorter in the negative group than in the negative group. The results suggest that PD-L1 expression is an independent prognostic factor.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R735.2

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