本文關(guān)鍵詞： 胃腫瘤 腫瘤免疫 PD-L1 PD-1 預(yù)后　出處：《安徽醫(yī)科大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:檢測PD-L1和PD-1在胃癌組織中的表達情況,探討其與患者臨床病理特征和預(yù)后生存的關(guān)系。方法:收集安徽醫(yī)科大學(xué)第一附屬醫(yī)院2007~2009年期間218例行胃癌根治術(shù)患者的腫瘤石蠟組織標本及其對應(yīng)的臨床病例資料,有淋巴結(jié)轉(zhuǎn)移的113例收集其轉(zhuǎn)移淋巴結(jié)標本,并隨機選取其中20例距腫瘤組織5 cm的癌旁組織作為對照組。采用免疫組織化學(xué)PV-6000兩步法檢測其中PD-L1和PD-1蛋白表達,采用染色強度分級和陽性細胞密度分級的乘積評定PD-L1表達,采用細胞計數(shù)法評估PD-1表達,采用SPSS17.0統(tǒng)計軟件分析其與患者各項臨床指標及預(yù)后的關(guān)系。結(jié)果:1.胃癌組織中PD-L1蛋白表達陽性率為66.97%,主要定位在胃癌細胞和癌間質(zhì)淋巴細胞的細胞質(zhì)和細胞膜,其中癌細胞上表達陽性率為66.05%,癌間質(zhì)淋巴細胞上表達陽性率為33.94%;PD-1蛋白表達陽性率為40.83%,主要定位在腫瘤浸潤淋巴細胞(TIL)的細胞質(zhì)和細胞膜;20例癌旁組織均無PD-L1和PD-1蛋白表達。轉(zhuǎn)移淋巴結(jié)中PD-L1和PD-1蛋白有表達,并且與其對應(yīng)的原發(fā)腫瘤組織表達高度一致,一致率分別為76.1%和86.7%。2.胃癌組織中癌間質(zhì)浸潤的淋巴細胞上PD-L1表達與PD-1表達呈顯著正相關(guān)(P=0.006),而癌細胞上PD-L1表達與PD-1表達無顯著相關(guān)性(P0.05)。3.胃癌細胞中PD-L1表達與p TNM分期(P0.01)、浸潤層面(P0.01)、淋巴結(jié)轉(zhuǎn)移情況(P0.01)及脈管癌栓(P0.05)密切相關(guān),而胃癌間質(zhì)細胞中PD-L1表達僅與淋巴結(jié)轉(zhuǎn)移與否(P0.05)相關(guān)。胃癌組織中PD-1表達與各臨床病理特征均無顯著相關(guān)性。4.單因素COX回歸分析顯示,p TNM分期較晚、腫瘤大小較大、淋巴結(jié)轉(zhuǎn)移陽性及胃癌細胞上PD-L1過表達是影響預(yù)后的不良因素。多因素COX回歸分析顯示,p TNM分期、腫瘤大小、淋巴結(jié)轉(zhuǎn)移和癌細胞PD-L1表達是預(yù)后的獨立因素。Kaplan-Meier生存曲線分析顯示胃癌細胞及癌間質(zhì)中PD-L1表達與患者術(shù)后生存期均呈現(xiàn)顯著相關(guān),PD-L1陽性表達者較陰性者術(shù)后生存期短,log-rank檢驗生存率差異有統(tǒng)計學(xué)意義(P0.01)。胃癌組織中PD-1陽性表達與否與術(shù)后生存期無關(guān)。結(jié)論:1.胃癌組織中PD-L1和PD-1均有表達,并明顯高于癌旁組織,且癌間質(zhì)PD-L1表達與TIL中PD-1表達呈顯著正相關(guān),而癌細胞上PD-L1表達與PD-1表達無顯著相關(guān)性。2.胃癌轉(zhuǎn)移淋巴結(jié)中PD-L1和PD-1均有表達,與其原發(fā)部位的表達情況具有高度一致性。3.胃癌細胞中PD-L1表達與多項臨床病理特征密切相關(guān),而胃癌間質(zhì)細胞中PD-L1表達僅與淋巴結(jié)轉(zhuǎn)移與否相關(guān)。胃癌組織中PD-1表達與各臨床病理特征均無顯著相關(guān)性。4.PD-L1陽性表達的胃癌患者較陰性者術(shù)后生存期短,提示PD-L1表達是影響預(yù)后的獨立因素。
[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.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R735.2

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