PD-L1表达对晚期肺腺癌患者培美曲塞化疗效果的影响及其机制  

Effect of PD-L1 expression on the efficacy of pemetrexed-based chemotherapy in patients with advanced lung adenocarcinoma and its mechanism

作　　者：施茂林 柏玉娣 王超 李思琪 周代君 彭晶晶 孙非凡 李东 张涛[1,2] SHI Maolin;BAI Yudi;WANG Chao;LI Siqi;ZHOU Daijun;PENG Jingjing;SUN Feifan;LI Dong;ZHANG Tao(Clinical Medical College,Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of Oncology,the General Hospital of Western Theater Command PLA,Chengdu 610083,Sichuan Province,China;Department of Pathology,the General Hospital of Western Theater Command PLA,Chengdu 610083,Sichuan Province,China;Medical College,Southwest Jiao Tong University,Chengdu 611756,Sichuan Province,China)

机构地区：[1]西南医科大学临床医学院,四川泸州646000 [2]中国人民解放军西部战区总医院肿瘤诊治中心,四川成都610083 [3]中国人民解放军西部战区总医院病理科,四川成都610083 [4]西南交通大学医学院,四川成都611756

出　　处：《中国癌症杂志》2021年第4期308-316,共9页China Oncology

基　　金：国家自然科学基金(81101634,81700766);四川省科技厅科技支撑计划(2017SZ0066,2015FZ0073)。

摘　　要：背景与目的:肺癌组织程序性死亡配体-1(programmed death ligand-1,PD-L1)表达水平不仅是程序性死亡[蛋白]-1(programmed death-1,PD-1)/PD-L1抑制剂最主要的疗效预测生物标志物,还可能影响表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)的疗效。然而,肺癌组织PD-L1表达水平能否影响肺腺癌患者化疗效果,目前相关文献报道较少。探讨肺腺癌组织PD-L1表达对培美曲塞为基础的化疗效果的影响及其潜在机制。方法:2015年10月—2018年12月于中国人民解放军西部战区总医院肿瘤诊治中心确诊为肺腺癌且符合研究入组条件的患者共185例。应用免疫组织化学法分别检测肺腺癌组织中PD-L1和培美曲塞疗效预测分子胸苷酸合酶(thymidylate synthase,TS)的表达。采用Kaplan-Meier法绘制患者的生存曲线,采用log-rank检验和COX回归模型分析影响患者无疾病进展生存(progression-free survival,PFS)的临床病理学因素,采用log-rank检验分别分析PD-L1和TS表达对患者PFS和总生存(overall survival,OS)的影响,采用Spearman秩相关性检验分析肺腺癌组织中PD-L1表达与TS表达的相关性。应用蛋白质印迹法(Western blot)及实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)分别检测6种肺腺癌细胞系中PD-L1、TS的蛋白水平和mRNA表达。采用Pearson相关性检验分析PD-L1和TS在蛋白表达水平及mRNA表达水平的相关性。结果:在51例一线接受培美曲塞为基础化疗的晚期肺腺癌患者中,PD-L1表达阳性患者的客观有效率(objective response rate,ORR)和疾病控制率(disease control rate,DCR)与PD-L1表达阴性患者相比差异无统计学意义(ORR:20.0%vs 35.5%,χ~2=1.404,P=0.236;DCR:60.0%vs 80.6%,χ~2=2.602,P=0.107)。PD-L1表达阴性患者的中位无疾病进展生存(median progression-free survival,mPFS)显著优于PD-L1表达阳性患者(mPFS:5.6个�Background and purpose:The expression of programmed death ligand-1(PD-L1)in lung cancer not only is the most important biomarker for predicting the efficacy of programmed death-1(PD-1)/PD-L1 inhibitors,but also may affect the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs)targeted therapy.However,there are currently few reports in the relevant literature on whether the expression of PD-L1 in lung cancer can affect the efficacy of chemotherapy in patients with lung adenocarcinoma.This study mainly explored the effect of PD-L1 expression in lung adenocarcinoma on the efficacy of pemetrexed-based chemotherapy and its underlying mechanism.Methods:From Oct.2015 to Dec.2018,185 eligible lung adenocarcinoma patients treated in Department of Pathology,The General Hospital of Western Theater Command PLA were enrolled.The expressions of PD-L1 and thymidylate synthase(TS),a molecule predicting the efficacy of pemetrexed-based chemotherapy,were detected by immunohistochemistry.The survival curve of patients was drawn by Kaplan-Meier method.The log-rank test and COX regression model were used to analyze the clinicopathological factors affecting the patients’progression-free survival(PFS)and overall survival(OS).The log-rank test was used to analyze the effects of PD-L1 and TS expressions on the patients’PFS and OS.Spearman rank correlation test was used to analyze the correlation between PD-L1 expression and TS expression in lung cancer tissues.Western blot and real-time fluorescent quantitative polymerase chain reaction(RTFQ-PCR)were used to detect the protein and mRNA expressions of PD-L1 and TS in 6 types of lung adenocarcinoma cell lines.The Pearson correlation test was used to analyze the correlation between PD-L1 and TS at protein expression level and mRNA expression level.Results:Among 51 patients with advanced lung adenocarcinoma who received pemetrexed-based chemotherapy as first-line treatment,the objective response rate(ORR)of the PD-L1 positive group was 20.0%,and the disease

关 键 词：肺腺癌 PD-L1 胸苷酸合酶 培美曲塞 

分 类 号：R734.2[医药卫生—肿瘤]