Study On Key Genes Of Lung Adenocarcinoma Based On Data Integration Strategy

Background: Lung cancer ranks first in morbidity and mortality among malignances in China.About 85% of lung cancer types are non-small cell lung cancer(NSCLC),among which the most common pathological type is lung adenocarcinoma(LUAD).Poor prognosis with a 5-year overall survival rate of less than 20% makes it urgent to elucidate underlying molecular mechanism of LUAD.Identifying potential therapeutic targets will surely benefit for early diagnosis and clinical treatment for LUAD.Through systematic bioinformatics analysis,in this study we tried to identify potentially functional key gene modules,core genes and crucial signaling pathway closely related to origin of LUAD.Methods: Four independent sets of expression data from GEO database are analyzed by bioinformatics methods,such as differential gene expression analysis,weighted gene co-expression network analysis and gene set enrichment analysis.Among them,the gene set enrichment analysis method is used to identify and find the important pathways closely related to the origin of LUAD.GO analysis,KEGG pathway analysis and DO enrichment are used to reveal the biological processes and potentially related diseases associated with LUAD.Through integrated weighted gene co-expression network analysis and differential gene expression analysis,we tried to explore functional key gene modules and hub genes closely related to LUAD.Then the survival analysis was used to evaluate significance of identified genes.Through the multi-dataset verification of Oncomine database,key genes related to pathogenesis of LUAD were delineated.Finally,the corresponding prognosis model was constructed.Results: Through gene enrichment analysis,it was found that there were 10 pathways closely related to LUAD with statistical significance.The significantly upregulated pathways include cell cycle,pyrimidine metabolism,DNA replication,base excision repair,and mismatch repair while the down-regulated pathways involve complement and coagulation cascades,vascular smooth muscle contraction,chemokine signaling pathway,hypertrophic cardiomyopathy,cell adhesion molecules.A total of 10 key genes were identified by combining WGCNA,DEGA and single factor COX analysis.Though preliminary verification using multiple datasets in Oncomine and prognosis model construction,it was found that only 3 genes(DOCK4,GOLM1,VIPR1)were closely related to the survival of LUAD patients.Conclusion: This study investigated genes,pathways and important functional gene modules related to pathogenesis of LUAD,providing clues for revealing molecular mechanism of LUAD.If the identified prognosis-related genes were confirmed by experiment,they will serve as potential biomarkers or therapeutic targets for LUAD.