拓扑异构酶Ⅱα与非小细胞肺癌预后及免疫浸润相关性的研究  

Analysis of correlation between topoisomeraseⅡalpha and the prognosis and immune infiltration in non-small cell lung cancer

作　　者：刘钟桧 朱青 刘新民[1] 焦红梅[1] LIU Zhong-hui;ZHU Qing;LIU Xin-min;JIAO Hong-mei(Department of Geriatrics,Peking University First Hospital,Beijing 100034,China;DepartmentofInternal Medicine,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200001,China)

机构地区：[1]北京大学第一医院老年病内科,北京100034 [2]上海交通大学医学院附属仁济医院内科,上海200001

出　　处：《中国临床药理学杂志》2025年第4期565-569,共5页The Chinese Journal of Clinical Pharmacology

基　　金：北京大学第一医院交叉研究专项课题资助项目(2024IR40)。

摘　　要：目的用生物信息学方法分析拓扑异构酶Ⅱα(TOP2A)基因与肺癌预后及免疫细胞浸润的相关性。方法用肿瘤免疫估算资源(TIMER)数据库分析肺癌患者TOP2A的表达差异。通过Kaplan-Meier Plotter和PrognoScan数据库评估TOP2A表达与肺癌预后的相关性。用TIMER数据库分析免疫浸润相关基因标记集与TOP2A表达的相关性。分别通过GeneMANIA和STRING工具构建基因和蛋白质之间的相互作用网络。通过miRWalk和DIANA-LncBase v2数据库分析TOP2A可能的表达调控网络。结果TOP2A在肺腺癌及鳞癌中的表达显著上调,且高TOP2A表达与肺癌患者的总生存期、首次进展生存期和进展后生存期降低显著相关。TOP2A的表达与肺癌中多种免疫细胞浸润显著相关,包括单核细胞、中性粒细胞、肿瘤相关巨噬细胞、辅助T细胞1、调节T细胞和耗竭T细胞。此外,TOP2A相关的基因或蛋白质网络主要与基因转录和细胞周期的调节有关,一个长链非编码RNA(lncRNA)ENSG00000279978被确定与肺腺癌和肺鳞癌的发展有关。结论TOP2A是肺癌预后及免疫浸润相关的生物标志物,可能成为肺癌免疫治疗的潜在靶点。Objective To analyze the correlations between topoisomeraseⅡalpha(TOP2A)and prognosis and immune infiltration in lung cancer.Methods The expression difference of TOP2A in lung cancer patients was examined by tumor immune estimation resource(TIMER)database.The prognostic value of TOP2A in lung cancer was evaluated using the Kaplan-Meier Plotter and PrognoScan databases.Additionally,the correlation between immune infiltration related gene marker sets and TOP2A expression was analyzed by TIMER database.The gene-gene and protein-protein interactions were determined using GeneMANIA and STRING for network construction,respectively.The possible regulatory network of TOP2A was explored by miRWalk and DIANA-LncBase v2 databases.Results The expression of TOP2A in lung adenocarcinoma(LUAD)and squamous cell carcinoma(LUSC)was significantly upregulated and high expression of TOP2A was significantly associated with reduced overall survival,first progression survival,and post-progression survival in lung cancer patients.TOP2A expression was significantly correlated with the infiltration of immune cells in lung cancer,including monocytes,neutrophils,tumor-associated macrophages,helper T cells 1,regulatory T cells,and exhausted T cells.The majority of genes or proteins associated with TOP2A were involved in the regulation of gene transcription and cell cycle.An lncRNA(ENSG00000279978)was identified as being related to the progression of LUAD and LUSC.Conclusion TOP2A is an immune infiltration-related prognostic biomarker for lung cancer and may serve as a potential therapeutic target.

关 键 词：拓扑异构酶Ⅱα 肺癌 免疫浸润 预后 生物标志物 

分 类 号：R97[医药卫生—药品]