TOP2A在肺腺癌中的表达及相关免疫机制

Expression of TOP2A in lung adenocarcinoma and its relation with prognosis of patients

目的研究拓扑异构酶2-α(TOP2A)在肺腺癌(LUAD)中的表达及其对LUAD患者生存预后的影响。方法通过Oncomine、TIMER数据库获取TOP2A在不同类型癌组织中的表达情况。通过Oncomine、GEPIA、GEO、Ualcan数据库获取TOP2A在LUAD中的表达水平。利用Ualcan数据库分析TOP2A在不同临床病理特征LUAD中的表达差异。利用Kaplan-Meier生存曲线评估TOP2A表达对LUAD患者总生存率的影响。利用HPA数据库分析TOP2A在LUAD组织中的蛋白质表达水平。利用cBioPortal数据库获取TOP2A基因突变信息及对LUAD患者预后的影响。利用TIMER数据库分析LUAD中TOP2A表达与免疫细胞(B细胞、CD4^(+)T细胞、CD8^(+)T细胞、中性粒细胞、巨噬细胞、树突状细胞)浸润的相关性。利用TISIDB数据库分析TOP2A的表达与趋化因子及免疫检查点调节剂的关系。结果TOP2A在肺癌、膀胱癌、乳腺癌、胆管癌等多种癌组织中高表达(均P<0.05)。TOP2A在LUAD中的表达水平明显高于正常组织(P<0.05),在不同人种、性别、年龄、吸烟史等临床病理特征中的表达差异均有统计学意义(均P<0.05)。TOP2A蛋白在LUAD组织中高表达。TOP2A过表达组的LUAD患者总生存率低于低表达组(P<0.05),TOP2A突变组LUAD患者总生存率明显降低(P<0.05)。TOP2A表达水平与B细胞、CD8^(+)T细胞及中性粒细胞浸润水平显著相关(均P<0.05),和多种趋化因子、免疫增强剂基因及免疫抑制剂基因均有相关性(均P<0.05)。结论TOP2A是LUAD预后的生物标志物,可能通过肿瘤免疫机制影响LUAD的发生、发展。

Objective To investigate the expression of topoisomerase II alpha(TOP2A)in lung adenocarcinoma(LUAD)and its relation with the survival and prognosis of patients with LUAD.Methods The expression of TOP2A in different types cancer tissues was obtained from Oncomine and TIMER database.The expression levels of TOP2A in LUAD were obtained from Oncomine,GEPIA,GEO and Ualcan databases.Ualcan database was used to analyze the expression levels of TOP2A in LUAD patients with different clinicopathological features.Kaplan-meier survival curve was used to evaluate the association of TOP2A expression with overall survival(OS)of LUAD patients.The protein expression levels of TOP2A in LUAD tissues were obtained from HPA database.The TOP2A mutation information and its effect on the prognosis of LUAD were obtained from cBioPortal database.TIMER database was used to analyze the correlation between the expression of TOP2A and immune-infiltrating cells(B cells,CD4^(+)T cells,CD8^(+)T cells,neutrophils,macrophages and dendritic cells)in LUAD patients.The relationship between TOP2A expression and chemokines and immunomodulators was analyzed from TISIDB database.Results The Oncomine and TIMER database showed that TOP2A was highly expressed in lung cancer,bladder cancer,breast cancer,bile duct cancer and other cancer tissues(all P<0.05).Based on Oncomine,Ualcan,GEPIA and GSE31210 databases,the expression levels of TOP2A in LUAD was significantly higher than that in normal tissues(P<0.05).The Ualcan database analysis showed that the expression of TOP2A mRNA was increased in LUAD patients with different race,sex,age and smoking history(all P<0.05).Kaplan-meier survival curve showed that the OS of LUAD patients in the TOP2A overexpression group was lower than that in the low expression group(P<0.05).The HPA database results indicated that TOP2A protein was highly expressed in LUAD tissues.The results of cBioPortal database suggested that the OS of LUAD patients in TOP2A gene mutation group was significantly decreased(P<0.05).Based on TIMER database,the expression of TOP2A was significantly correlated with B cells,CD8^(+)T cells and neutrophil infiltration levels(all P<0.05).The TISIDB database results indicated that the expression of TOP2A was correlated with a variety of chemokines,immunostimulator genes and immunoinhibitor genes in LUAD(all P<0.05).Conclusion TOP2A may be a prognostic biomarker of LUAD,which might influence the occurrence and development of LUAD through tumor immune mechanism.