非小细胞肺癌组织中PD-1/PD-L1的表达与EGFR突变的关系及其对预后的影响

Relationship between the expression of PD-1/PD-L1 and EGFR mutation in non-small cell lung cancer and its effect on prognosis

目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)中程序性死亡受体1(programmed death receptor-1,PD-1)及程序性死亡受体配体1(programmed death receptor ligand-1,PD-L1)的表达和EGFR突变及其与预后的关系。方法:收集2013年01月至2015年12月由我院病理科经组织学诊断为非小细胞肺癌,并完成EGFR突变检测的150例患者的临床资料,应用免疫组织化学方法检测NSCLC组织中PD-1/PD-L1和CD8蛋白表达情况,分析其与临床病理参数及与EGFR突变的相关性,并对影响患者预后的多个临床病理因素进行分析。结果:非小细胞肺癌组织中PD-1/PD-L1和CD8的阳性表达率分别为34.7%(52/150)、50.4%(57/113)和59.2%(84/142)。其中PD-L1的表达与PD-1的表达(P=0.025,r_(s)=0.211)有关;PD-1的表达与术后病理分期(P=0.031,r_(s)=-0.177)及EGFR突变(P=0.001,r_(s)=-0.257)和CD8的表达(P=0.000,r_(s)=0.323)有关;CD8的表达与组织学类型(P=0.048,r_(s)=0.173)有关。对NSCLC患者随访,肿瘤中-低分化程度、临床分期Ⅳ期、存在远处转移及PD-1高表达的患者总生存期分别低于肿瘤高分化程度、临床分期I-III期、不存在远处转移及PD-1低表达的患者(均P<0.05)。结论:PD-1/PD-L1和CD8参与NSCLC的病理过程,PD-1的表达与非小细胞肺癌患者术后病理分期及EGFR突变状态有关,影响患者预后。

Objective:To study the prognostic significance of programmed death receptor-1(PD-1),programmed death receptor ligand-1(PD-L1)with EGFR mutation in predicting non-small cell lung cancer(NSCLC)patients'survival time.Methods:The clinical data of 150 patients with histologically diagnosed NSCLC who complete EGFR mutation detection in our hospital from January 2013 to December 2015 were collected.The expressions of PD-1/PD-L1 and CD8 proteins in NSCLC tissues were detected by immunohistochemistry.The correlation between EGFR mutation and clinicopathological parameters were analyzed,with the clinicopathological factors affecting the prognosis of patients.Results:The positive expression rates of PD-1/PD-L1 and CD8 in NSCLC tissues were 34.7%(52/150),50.4%(57/113)and 59.2%(84/142),respectively.The expression of PD-L1 was correlated with the expression of PD-1(P=0.025,Spearman correlation coefficient 0.211).The expression of PD-1 was correlated with postoperative pathological stage(P=0.031,Spearman correlation coefficient-0.177),EGFR mutation(P=0.001,Spearman correlation coefficient-0.257)and CD8 expression(P=0.000,Spearman correlation coefficient 0.323).The expression of CD8 was correlated with histological type(P=0.048,Spearman correlation coefficient 0.173).Follow-up of NSCLC patients showed that the overall survival of patients with moderate-poorly differentiated tumors,clinical stageⅣ,distant metastasis and high PD-1 expression were significantly lower than those with highly differentiated tumors,clinical stage I-III,no distant metastasis and low PD-1 expression(P<0.05).Conclusion:PD-1/PD-L1 and CD8 are involved in the pathological process of NSCLC.The expression of PD-1 is related to the postoperative pathological stage and EGFR mutation status of patients with NSCLC,which affects the prognosis of patients.