胃癌肿瘤突变负荷miRNA预测模型的构建和验证  

Construction and Validation of A MiRNAs Prediction Model for Tumor Mutational Burden in Gastric Cancer

作　　者：陈融 李伟娜[2] 姜相君[2] CHEN Rong;LI Weina;JIANG Xiangjun(Qingdao University,Qingdao,Shandong Province,266071;Department of Gastroenterology,Qingdao Municipal Hospital,Qingdao,Shandong Province)

机构地区：[1]青岛大学,266071 [2]青岛市市立医院消化内科

出　　处：《胃肠病学》2022年第4期232-238,共7页Chinese Journal of Gastroenterology

基　　金：2020年青岛市科技局项目(20⁃3⁃4⁃44⁃nsh);2020年青岛市市南区科技局项目(2020⁃2⁃010⁃YY);2020年青岛市医疗卫生A类重点学科(V市学科A2020Y04⁃2022)。

摘　　要：背景:肿瘤突变负荷(TMB)是一个很有前途的预测因子,可在一定程度上预测肿瘤患者应用免疫检查点抑制剂(ICI)治疗的效果。微RNA(miRNA)作为在抗癌免疫反应中的关键调节因子,与胃癌患者TMB之间的关系尚不明确。目的:通过分析TCGA数据库中胃癌患者测序数据和临床数据,构建胃癌患者TMB预测模型并加以验证。方法:将TCGA数据库中的胃癌患者分为高TMB组和低TMB组,筛选差异表达miRNA。将胃癌患者随机分为训练组和验证组,对训练组数据采用lasso回归分析法构建预测TMB水平的miRNA预测模型,并使用验证组数据进行验证。对筛选出的相关miRNA进行KEGG功能富集分析,并分析与3个ICI的相关性。结果:共筛选出54个差异表达miRNA,其中20个为TMB相关miRNA。MiRNA预测模型的敏感性、特异性、AUC均较高。功能富集结果表明,TMB相关的miRNA主要参与与免疫反应相关的生物学过程以及与癌症相关的信号通路。MiRNA预测模型与PD⁃L1(r=0.36,P<0.01)中度正相关,与PD⁃1(r=-0.31,P<0.01)中度负相关,与CTLA4无明显相关性(r=0.14,P<0.01)。结论:本研究构建了一种miRNA预测模型,可对不同TMB水平的胃癌患者进行分层。Background:Tumor mutational burden(TMB)is a promising predictor,which can evaluate the efficacy of immune checkpoint inhibitors(ICIs)for tumor patients.MicroRNAs(miRNAs)act as the key regulators of anti⁃cancer immune response.However,the relationship between TMB and miRNAs expression profiles in gastric cancer is not elucidated.Aims:To construct and validate the TMB prediction model of gastric cancer by analyzing the sequencing data and clinical data in TCGA database.Methods:Gastric cancer patients in TCGA database were divided into TMB high group and TMB low group,and differentially expressed miRNAs were screened.Gastric cancer patients were randomly divided into training group and validation group.A miRNAs prediction model for predicting TMB level was developed by lasso regression analysis method in training group,and was validated in validation group.KEGG functional enrichment analysis was used to analyze the screening related miRNAs.The correlation between miRNAs and three ICIs was analyzed.Results:Fifty⁃four differentially expressed miRNAs were screened,and 20 of them were identified as TMB⁃related miRNAs.The sensitivity,specificity,AUC in the miRNAs prediction model were relatively high.Functional enrichment results revealed that TMB⁃related miRNAs were mainly involved in biological process associated with immune response and signaling pathways related with cancer.The miRNAs prediction model showed a median positive correlation with PD⁃L1(r=0.36,P<0.01),a median negative correlation with PD⁃1(r=-0.31,P<0.01)and no significant correlation with CTLA4(r=0.14,P<0.01).Conclusions:This study presents a miRNAs prediction model which can stratify gastric cancer patients with different TMB levels.

关 键 词：胃肿瘤 免疫检查点抑制剂 微RNAS 肿瘤突变负荷 

分 类 号：R735.2[医药卫生—肿瘤]