基于lncRNA-mRNA共表达网络筛选胃癌分期相关的lncRNA

The Screening of LncRNA Related to Staging of Gastric Cancer based on LncRNA-mRNA Co-expression Network

目的构建lncRNA-mRNA共表达网络,探索与胃癌分期相关的lncRNA及其调控关系,为研究胃癌的进展机制及寻找胃癌治疗的潜在靶点提供依据。方法利用TCGA数据库,收集胃癌RNA-seq数据及临床信息数据;采用表达数量性状位点(eQTL)分析与加权基因共表达网络分析(WGCNA)相结合的方法,构建lncRNA-mRNA共表达网络模块,结合临床信息筛选与胃癌分期相关的模块;采用Kruskal-Wallis秩和检验筛选模块内胃癌不同分期差异表达的lncRNA。结果获得286例胃癌组织和30例癌旁对照组织样本的RNA-seq数据;eQTL分析得到5118对顺式作用和1 953 109对反式作用lncRNA-mRNA;2 999个lncRNA和3 884个mRNA纳入WGCNA,产生25个共表达模块,其中与胃癌分期高度相关的模块有3个;模块midnightblue、orange内18个枢纽lncRNA中有14个lncRNA在胃癌不同分期差异表达。结论本研究筛选出14个与胃癌分期相关的lncRNA,这14个lncRNA可能通过调控mRNA的表达影响胃癌的进展,分析其对应的网络调控关系,为研究lncRNA-mRNA调控机制及探索胃癌治疗靶点提供了参考和方向。

Objective The main idea is to construct lncRNA-mRNA co-expression network to explore the lncRNA related to staging of gastric cancer and its regulatory relationship, providing a basis for the study of the mechanism of gastric cancer progression and the search for potential therapeutic target.Methods RNA-seq data and clinical information data of gastric cancer was collected by TCGA database.Combining expression quantitative trait locus(eQTL)analysis with weighted gene co-expression network analysis(WGCNA)to construct lncRNA-mRNA co-expression network module, screening the modules related to gastric cancer staging.Kruskal-Wallis rank sum test was used to test the lncRNA differentially expressed in different stages of gastric cancer.Results We have obtained the RNA-seq data of 286 gastric cancer tissues and 30 paracancer control tissues.Through eQTL analysis, 5118 cis and 1 953 109 trans lnc-eQTL pairs were obtained.2 999 lncRNAs and 3 884 mRNAs were incorporated into WGCNA,generating 25 co-expression modules, among which 3 modules were highly correlated with staging of gastric cancer.Fourteen lncRNAs were differentially expressed in different stages of gastric cancer among the 18 hub lncRNAs in midnightblue and orange module.Conclusion In this study, fourteen lncRNAs related to staging of gastric cancer were screened out, which may influence the progress of gastric cancer by regulating the expression of mRNA,analyzing the network regulation relationship providing reference and direction for the study of the regulation mechanism of lncRNA-mRNA and the exploration of therapeutic targets for gastric cancer.