摘要
目的 分析免疫检查点基因(PD-1、PD-L1、CTLA4、LAG3、FGL1、TIGIT、TIM-3、SIGLEC-15、IDO1、CD276、CD70、VTCN1、CD47、TNFSF14、TNFRSF18)在肺腺癌和肺鳞癌中的表达及临床与生物学意义.方法 从TCGA数据库中获取肺腺癌、肺鳞癌的免疫检查点基因表达数据及临床信息.采用Wilcoxon符号秩检验比较免疫检查点基因在肿瘤组织与正常组织的表达差异,通过主成分分析构建免疫检查点基因评分系统,采用单因素及多因素Cox回归分析肺腺癌、肺鳞癌的预后影响因素,然后进行通路富集分析.结果 肺腺癌中PD-1、CTLA4、LAG3、FGL1、TIGIT、SIGLEC-15、CD276、CD70、VTCN1 以及 TNFRSF18 的表达显著高于正常组织(P＜0.01,P＜0.05),PD-L1、TIM-3、CD47 以及 TNFSF14 的表达显著低于正常组织(P＜0.01,P＜0.05),TIGIT与肺腺癌的T分期、N分期、M分期显著相关(P＜0.05),CTLA4与肺腺癌的OS成正相关(P＜0.05);肺鳞癌中 CD276、CD70、VTCN1、TNFRSF18 的表达显著高于正常组织(P＜0.05),PD-L1、TIM-3、IDO1、CD47、TNFSF14的表达显著低于正常组织(P＜0.05),VTCN1与肺鳞癌的N分期显著相关(P＜0.05),TIM-3与肺鳞癌OS、PFS成负相关(P＜0.05).LUAD-Im评分和LUSC-Im评分分别是肺腺癌和肺鳞癌OS、PFS的独立危险因素(P＜0.05).结论 免疫检查点基因与肺腺癌和肺鳞癌的临床病理特征及预后密切相关,免疫检查点基因综合评分是一种可行的用于预测肺腺癌、肺鳞癌预后的方法.
Abstract
Objective To analyze the expression and clinical and biological significance of immune checkpoint genes(PD-I,PD-L1,CTLA4,LAG3,FGL1,TIGIT,TIM-3,SIGLEC-15,IDO1,CD276,CD70,VTCN1,CD47,TNFSF14,and TNFRSFI8,in lung adenocarcinoma and lung squamous cell carcinoma.Methods The immune checkpoint gene expression data and clinical information of lung adenocarcinoma and lung squamous cell carcinoma were obtained from TCGA database.Wilcoxon signed-rank test was used to compare the expression difference of immune checkpoint genes in tumor tissues and normal tissues.A comprehensive scoring system for immune checkpoint genes was constructed through principal component analysis.Univariate and multivariate Cox regressions were used to analyze the prognostic factors of lung adenocarcinoma and lung squamous cell carcinoma,and then pathway enrichment analysis was done.Results The expressions of PD-1,CTLA4,LAG3,FGL1,TIGIT,SIGLEC-15,CD276,CD70,VTCN1 and TNFRSF18 in lung adenocarcinoma were significantly higher than those in normal tissues(P＜0.01,P＜0.05),and the expressions of PD-L1,TIM-3,CD47 and TNFSF14 were significantly lower than those in normal tissues(P＜0.01,P＜0.05).TIGIT was significantly correlated with the T,N,and M stages of lung adenocarcinoma(P＜0.05),and CTLA4 was positively correlated with the OS of lung adenocarcinoma(P＜0.05).In lung squamous cell carcinoma,the expressions of CD276,CD70,VTCN1,and TNFRSF18 were significantly higher than those in normal tissues(P＜0.05),and the expressions of PD-L1,TIM-3,IDO1,CD47,and TNFSF14 were significantly lower than those in normal tissues(P＜0.05).VTCN1 was significantly correlated with the N stage of lung squamous cell carcinoma(P＜0.05),and TIM-3 was negatively correlated with OS and PFS of lung squamous cell carcinoma(P＜0.05).LUAD-Im score and LUSC-Im score were independent risk factors for OS and PFS of lung adenocarcinoma and lung squamous cell carcinoma,respectively(P＜0.05).Conclusion The immune checkpoint genes are closely related to the clinicopathological features and prognosis of lung adenocarcinoma and lung squamous cell carcinoma.The comprehensive score of immune checkpoint genes is a feasible method for predicting the prognosis of lung adenocarcinoma and lung squamous cell carcinoma.
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