肝细胞癌肿瘤微环境细胞毒性T细胞PD-1的表达及其临床意义  

Expression and clinical significance of microenvironment cytotoxic T cells PD-1 in hepatocellular carcinoma

作　　者：龚解其 沈卫星 陆欢华 GONG Jie-qi;SHEN Wei-xing;LU Huan-hua(Department of General Surgery,FuDan Univerisity Afflicated Zhongshan Hospital Qingpu Branch,Shanghai 201700,China)

机构地区：[1]复旦大学附属中山医院青浦分院普外科,上海201700

出　　处：《临床和实验医学杂志》2024年第1期5-9,共5页Journal of Clinical and Experimental Medicine

基　　金：上海市青浦区科技局项目(编号:QKY2021-07);上海市卫健委项目(编号:w2020-11)。

摘　　要：目的探讨程序性细胞死亡蛋白1(PD-1)在肝细胞癌(HCC)肿瘤微环境细胞毒性T细胞中的表达及其临床意义。方法回顾性选取2012年1月至2020年12月入复旦大学附属中山医院青浦分院接受手术治疗的HCC患者344例为研究对象,手术切除HCC患者的癌组织,免疫组织化学双染色法检测PD-1的表达,依据PD-1的表达中位数水平分为PD-1高表达和PD-1低表达,分析PD-1表达与临床病理参数的相关性,采用Kaplan-Meier方法计算总生存率和无进展生存率并绘制生存曲线,采用多因素Cox回归分析HCC的预后影响因素。结果PD-1表达于HCC肿瘤浸润淋巴细胞的细胞膜和(或)细胞质上,肿瘤浸润淋巴细胞中PD-1的高表达率为43.9%(151/344);HCC肿瘤组中PD-L1的阳性表达率为21.8%(75/344);HCC肿瘤浸润免疫细胞中PD-L1的阳性表达率为47.1%(162/344);肿瘤浸润CD8^(+)T细胞高密度率为45.3%(156/344)。PD-1高表达与肿瘤组织学分级、肿瘤细胞PD-L1表达、CD8^(+)T淋巴细胞PD-L1表达、CD8^(+)T淋巴细胞密度有关(P<0.05)。PD-1高表达患者的总生存率为80.81%,明显低于PD-1低表达患者(88.95%),差异有统计学意义(P<0.05)。PD-1高表达患者的无病生存率为67.44%,明显低于PD-1低表达患者(84.30%),差异有统计学意义(P<0.05)。多因素Cox回归分析结果显示,肿瘤细胞PD-L1表达、肿瘤浸润免疫细胞PD-L1表达、CD8^(+)T淋巴细胞密度均为影响肝细胞癌患者预后的危险因素(P<0.05)。结论CD8^(+)T淋巴细胞中PD-L1具有较高的表达率,CD8^(+)T细胞PD-1高表达与肿瘤组织学分级、肿瘤细胞PD-L1表达、CD8^(+)T淋巴细胞PD-L1表达、CD8^(+)T淋巴细胞密度、总生存率和无病生存率显著相关,可作为HCC患者辅助诊断和预测预后的指标之一。Objective To investigate the expression of programmed cell death protein 1(PD-1)in hepatocellular carcinoma(HCC)microenvironment cytotoxic T cells and its clinical significance.Methods A total of 344 HCC patients admitted to FuDan Univerisity Afflicated Zhongshan Hospital Qingpu Branch from January 2012 to December 2020 were retrospectively selected as the study subjects.The expression of PD-1 in the cancer tissues of surgically resected HCC patients was detected by immunohistochemical double staining,and divided into high PD-1 expression and low PD-1 expression according to the median expression level of PD-1.The correlation between PD-1 and clinicopathological features was analyzed.Kaplan-Meier method was used to calculate overall survival rate and progression-free survival rate,and survival curves were drawn.The prognostic factors of HCC was analyzed by using Multivariate Cox regression analysis.Results PD-1 was expressed on the cell membrane and/or cytoplasm of tumor infiltrating lymphocytes of HCC,and the high expression rate of PD-1 in tumor infiltrating lymphocytes was 43.9%(151/344).The positive expression rate of PD-L1 in HCC tumor group was 21.8%(75/344).The positive expression rate of PD-L1 in HCC tumor infiltrating immune cells was 47.1%(162/344).Tumor infiltrating CD8^(+)T cell density was 45.3%(156/344).The high expression of PD-1 was related to tumor histological grade,PD-L1 expression of tumor cells,PD-L1 expression of CD8^(+)T lymphocytes,and CD8^(+)T lymphocyte density(P<0.05).The overall survival rate of patients with high PD-1 expression was 80.81%,which was significantly lower than that of patients with low PD-1 expression(88.95%),and the difference was statistically significant(P<0.05);The disease-free survival rate of patients with high PD-1 expression was 67.44%,which was significantly lower than that of patients with low PD-1 expression(84.30%),and the difference was statistically significant(P<0.05).Multivariate Cox regression analysis showed that PD-L1 expression in tumor cells,PD-L1 ex

关 键 词：肝细胞癌 程序性细胞死亡蛋白1 CD8^(+)T 程序性细胞死亡-配体1 预后 

分 类 号：R735.7[医药卫生—肿瘤]