LncRNA m6A修饰在肺鳞癌的预后及免疫疗效预测中的鉴定和价值分析  

Identification of m6A-related lncRNA Prognostic Signature and Its Prediction of Immunotherapy Efficacy in Lung Squamous Cell Carcinoma

作　　者：顾睿 莫春芬 林苹[1] 张洁[1] 李凯[1] Gu Rui;Mo Chunfen;Lin Ping;Zhang Jie;Li Kai(Lab of Experimental Oncology,Cancer Center,West China Hospital of Sichuan University,Chengdu 610041,China;Department of Immunology,School of Basic Medical Sciences,Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]四川大学华西医院肿瘤中心实验肿瘤研究室,成都610041 [2]成都医学院基础医学院免疫学教研室,成都610500

出　　处：《成都医学院学报》2022年第4期409-415,共7页Journal of Chengdu Medical College

基　　金：国家自然科学基金项目(No:82072933);四川大学华西医院1·3·5优秀学科项目-临床研究孵化项目(No:2020HXFH007)。

摘　　要：目的鉴定肺鳞癌患者的lncRNA m6A修饰联合预后标志物,并预测免疫检查点抑制剂(ICI)的疗效。方法从肿瘤基因组图谱(TCGA)数据库中下载肺鳞癌患者的转录组、体细胞突变及临床数据,基于单因素Cox回归分析及Lasso回归分析鉴定出13个lncRNA m6A修饰联合预后标志物,建立预后风险模型,并从生存率等角度评估该预后风险模型的预测效能,通过肿瘤免疫功能障碍和排斥(TIDE)及肿瘤微环境(TME)分析验证其预测免疫疗效的可靠性。结果鉴定出13个具有预后意义的lncRNA m6A修饰,并用于构建预后风险模型。Kaplan-Meier(K-M)曲线显示,高风险组患者的预后较低风险组患者更差;单因素、多因素Cox回归分析显示,风险评分为独立预后因素;此外,风险评分与TIDE、TME相关。结论本研究鉴定出的lncRNA m6A修饰联合预后标志物是肺鳞癌有效的独立预后指标,并为肺鳞癌患者ICI治疗的应用提供理论依据。Objective To identify long non-coding RNAs(lncRNAs)with m6A modification combined prognostic markers,which predicts the prognosis of patients with lung squamous cell carcinoma and the efficacy of immune checkpoint inhibitors(ICI).Methods Transcriptomic,somatic mutation and clinical data of patients with lung squamous cell carcinoma were downloaded from the Cancer Genome Atlas(TCGA)database,from which 13 pair prognostic markers of lncRNAs with m6A modification were identified and used to establish prognostic risk model based on univariate Cox regression analysis and Lasso regression analysis.The validity of the prognostic risk model was evaluated from the perspectives of survival rate,etc.And the reliability of the model in predicting the efficacy of immunotherapy was verified by tumor immune dysfunction and exclusion(TIDE)and tumor microenvironment(TME)analysis.Results A total of 13 lncRNAs with m6A modification with significant prognostic significance were identified and used to construct prognostic risk models.Kaplan-Meier(KM)curve showed that patients in the high-risk group had a worse prognosis than those in the low-risk group.Besides,univariate and multivariate Cox regression analysis showed that the risk score was an independent prognostic factor.In addition,risk scores were associated with TIDE and TME.Conclusion It is illustrated that 13 lncRNAs with m6A modification combined prognostic markers are effective independent prognostic indicators of lung squamous cell carcinoma,which provides theoretical basis for ICI treatment for patients with lung squamous cell carcinoma.

关 键 词：lncRNA M6A 肺鳞癌 预后 免疫治疗 

分 类 号：R734.2[医药卫生—肿瘤]