PD-1和PD-L1的表达与胃癌患者临床病理特征及预后的相关性Meta分析

Meta-analysis on the correlation between the expression of PD-1,PD-L1 and clinicopathological features and prognosis of patients with gastric cancer

目的评估程序性死亡受体1(PD-1)及程序性死亡受体1配体(PD-L1)的表达与胃癌患者临床病理特征及预后的相关性。方法检索中国生物医学文献数据库、中国知网、万方及PubMed、embase、web of science、Cochrance library自建库以来的所有相关研究,截止日期为2017年12月,同时辅以手工检索和其他检索方式。根据Newcastle-Ottawa Scale(NOS)文献质量评价量表评价文献质量。采用Stata14.0统计软件对数据进行统计分析,采用比值比(OR)及其95%置信区间(CI)分析PD-1及PD-L1的表达与患者临床病理特征的相关性;采用相对危险度(RR)及其95%CI分析PD-1及PD-L1的表达与患者预后的相关性;采用Egger检验、Begg检验评估发表性偏倚。结果纳入11篇文献,共计患者2 940例。PD-1的表达与淋巴结转移、淋巴管浸润有明显相关性,但与性别、肿瘤大小、分化程度、Lauren分型、T分期、血管浸润、M分期、TNM分期无明显相关性; PD-L1的表达与淋巴结转移、淋巴管浸润、血管浸润有明显相关性,但与性别、分化程度、T分期、TNM分期无明显相关性。PD-1阳性患者与阴性患者的3年生存率(RR=1.12,95%CI 0.85～1.48,P=0.432)、5年生存率(RR=1.14,95%CI 0.93～1.39,P=0.207)比较差异均无统计学意义; PD-L1阳性患者与阴性患者的3年生存率(RR=1.40,95%CI 0.90～2.17,P=0.138)、5年生存率(RR=1.29,95%CI 0.96～1.74,P=0.090)比较差异均无统计学意义。结论胃癌组织中PD-1和PD-L1的表达会增加癌细胞的侵袭力,可作为胃癌治疗的新靶点,阻断PD-1/PD-L1通路将成为胃癌免疫治疗的新突破口。

Objective To evaluate the correlation between expression of programmed death 1(PD-1),programmed death ligand-1(PD-L1)and clinicopathological features and prognosis of patients with gastric cancer.Methods We performed a search for all relevant studies since the establishment of Chinese Biomedical Database,China national knowledge internet,Wanfang database,PubMed,embase,web of science,Cochrance library,and the deadline was December 2017.Meanwhile,it was supplemented by manual search and other retrieval methods.Evaluation of document quality was based on Newcastle-Ottawa Scale(NOS)document quality assessment scale.The data were analyzed by Strata 14.0 software.The correlation between the expression of PD-1 and PD-L1 and clinicopathological features of the patients was analyzed by odds ratio(OR)and 95%confidence interval(CI).Relative risk(RR)and 95%CI were used to analyze the correlation between the expression of PD-L1 and PD-L1 and the prognosis of patients.Egger test and Begg test were used to assess publication bias.Results Eleven articles were included,with a total of 2 940 patients.The expression of PD-1 was significantly correlated with lymph node metastasis and lymphatic vessel infiltration,but not with sex,tumor size,differentiation degree,Lauren’s classification,T stage,vessel infiltration,M stage and TNM stage.The expression of PD-L1 was significantly correlated with lymph node metastasis,lymphatic vessel infiltration and vessel infiltration,but was not significantly correlated with sex,differentiation degree,T stage and TNM stage.There was no statistically significant difference between PD-1 positive and negative patients in three-year survival rate(RR=1.12,95%CI 0.85-1.48,P=0.432)and five-year survival rate(RR=1.14,95%CI 0.93-1.39,P=0.207).There was no statistically significant difference between PD-L1 positive and negative patients in three-year survival rate(RR=1.40,95%CI 0.90-2.17,P=0.138)and five-year survival rate(RR=1.29,95%CI 0.96-1.74,P=0.090).Conclusion The expression of PD-1 and PD-L1 in gastric cancer tissues can increase the invasiveness of cancer cells.It can be used as a new target for the treatment of gastric cancer,blocking the PD-1/PD-L1 pathway,and will become a new breakthrough in the immunotherapy of gastric cancer.