基于数据库LKB1突变肺腺癌DNA异常甲基化位点构建的预后风险模型  

A prognostic risk model for LKB1 mutant lung adenocarcinoma based on aberrant DNA methylation sites

作　　者：郑昊天 王光辉 赵小刚[3] 王亚东 曾榆凯 杜贾军 ZHENG Haotian;WANG Guanghui;ZHAO Xiaogang;WANG Yadong;ZENG Yukai;DU Jiajun(Institute of Oncology,Shandong Provincial Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250021,Shandong,China;Department of Thoracic Surgery,Shandong Provincial Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250021,Shandong,China;Department of Thoracic Surgery,The Second Hospital,Cheeloo College of Medicine,Shandong University,Jinan 250033,Shandong,China)

机构地区：[1]山东大学齐鲁医学院省立医院肿瘤研究所,山东济南250021 [2]山东大学齐鲁医学院省立医院胸外科,山东济南250021 [3]山东大学第二医院胸外科,山东济南250033

出　　处：《山东大学学报（医学版）》2022年第3期51-58,共8页Journal of Shandong University:Health Sciences

基　　金：山东省自然科学基金(ZR2021MH192);济南市临床医学科技创新计划(202019058)

摘　　要：目的构建DNA甲基化相关的肝激酶B1(LKB1)突变肺腺癌预后风险模型。方法下载并分析癌症基因组图谱(TCGA)数据库中RNA和甲基化测序数据。筛选甲基化调控显著影响预后的差异表达基因,构建预后风险模型,将LKB1突变肺腺癌患者分为高风险组和低风险组,并进行相关功能学分析。结果筛选出3个低甲基化高表达的预后相关基因并构建LKB1突变肺腺癌的预后风险模型。多因素COX回归分析表明,Risk score可作为独立预测因子(HR>2,P<0.001)。受试者工作特征曲线证实,Risk score比其他临床病理特征有更好的生存预测能力。功能分析表明,高风险LKB1突变肺腺癌患者促癌通路激活、免疫细胞浸润程度明显高于低风险患者。结论在LKB1突变肺腺癌中发掘了3个因异常甲基化而表达失调的分子标记物,据此构建的预后风险模型可以准确筛选LKB1突变肺腺癌患者中的高风险人群,提供生存预测,为LKB1突变肺腺癌的分子机制研究及临床预后分析提供新思路。Objective To construct a methylation-related prognostic risk model of liver kinase B1(LKB1)mutant lung adenocarcinoma.Methods The RNA and methylation sequencing data from the The Cancer Genome Atlas(TCGA)database were downloaded and analyzed.Differentially expressed genes that significantly affected the prognosis and were regulated by different methylation sites were screened out to construct a prognostic risk model.Then,the LKB1 mutant lung adenocarcinoma patients were divided into the high-risk group and low-risk group and the corresponding function was analyzed.Results Three prognostic-related genes with low methylation levels and high expression levels were screened out and a prognostic risk model of LKB1 mutant lung adenocarcinoma was constructed.Multivariate COX regression analysis showed that Risk score could be used as an independent predictor(HR>2,P<0.001).The receiver operating characteristic(ROC)curve confirmed that the Risk score had better survival predictive ability than other clinicopathological characteristics.The cancer-promoting pathway was activated in the high-risk group and the degree of immune cell infiltration was significantly higher than that in the low-risk group.Conclusion Three biomarkers due to aberrant methylation are discovered in LKB1 mutant lung adenocarcinomas.The prognostic risk model can accurately screen the high-risk population among patients with LKB1 mutant lung adenocarcinoma,and provides accurate survival predictions.The study provides new ideas for the molecular mechanism and the clinical prognosis analysis of LKB1 mutant lung adenocarcinoma.

关 键 词：肝激酶B1 肺腺癌 DNA甲基化 预后风险模型 癌症基因组图谱 

分 类 号：R734.2[医药卫生—肿瘤]