Integrated Analysis Of Key Genes With Prognostic Value In Non-small-cell Lung Cancer

Objective:Lung cancer is the most common cause of cancer-related death among all human cancers and the five-year survival rates are only 23%.Nowadays,the exact molecular mechanism of non-small cell lung cancer remains unknown.In this work,we aim to identify and validate the prognostic value of key genes with in non-small cell lung cancer.Methods:RNA transcriptome profiling data of LUAD and LUSC group were obtained from four GEO datasets(GSE18842,GSE33532,GSE62113,and GSE747068)in the Gene Expression Omnibus(GEO)database(https://www.ncbi.nlm.nih.gov/gds).Then,common differentially expressed genes(DEGs)of four GEO datasets were selected for KEGG pathway analysis and GO enrichment analysis.Next,we constructed protein-protein interaction(PPI)networks using the STRING database and visualized by Cytoscape software.Moreover,Molecular Complex Detection(MCODE)were utilized to pick out meaningful DEGs.Hub genes,filtered from the CytoHubba,were validated using the Gene Expression Profiling Interactive Analysis database.In addition,the expressions and prognostic values of hub genes were carried out by different database including Gene Expression Profiling Interactive Analysis(GEPIA),Oncomine database,cBioportal database and Kaplan-Meier plotter.Finally,the expression of hub genes in lung cancer cells and normal tissues were verify by quantitative PCR.Results:Total of 121 DEGs were identified from four GEO datasets.There are three pathways that enriched by upregulated DEGs including P53 signaling pathway,cell cycle and cellular senescence.Moreover,downregulated DEGs were notably enriched in ECM-receptor interaction,AGE-RAGE signaling pathway in diabetic complications,hypertrophic cardiomyopathy and dilated cardiomyopathy.The PPI network was established with 121 nodes and 588 protein pairs.Finally,AURKA,KIAA0101,CDC20,MKI67,CHEK1,HJURP,and OIP5 were selected by Cytohubba,and they all correlated with worse overall survival(OS)in NSCLC.Conclusion:Our study performed a systematic analysis on prognostic value of key gene in NSCLC.Our results showed that AURKA,KIAA0101,CDC20,MKI67,CHEK1,HJURP,and OIP5 may be significance genes in the development and prognosis of NSCLC.Our methods showed a novel way to explore the key genes in cancer research.