Identification of hub genes associated with prognosis of gastric cancer by integrated bioinformatics analysis

Abstract

Objective To identify the hub genes associated with development of gastric cancer (GC) by integrated bioinformatics analysis, and investigate whether these genes can be used as latent biomarkers of predicting GC prognosis. Methods The gastric cancer of microarray data was downloaded from the Gene Expression Omnibus (GEO) database (GSE79973), and the transcriptome data and corresponding clinical data of GC patients were obtained from The Cancer Genome Atlas (TCGA) database. Differential gene expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) were performed on the dataset using the Limma and WGCNA packages in the R software, respectively, in order to screen differentially co-expressed genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differential co-expression genes were performed using the ClusterProfler package. The search tool for the retrieval of interacting genes (STRING) was carried out the protein-protein interaction (PPI) network of differential co-expression genes, and the software Cytoscape was used to visualize and screen out hub genes. The transcriptional expression of the hub gene was further verified by GEPIA2 database. Survival analysis was performed by using the survival package in R software to identify prognostic hub genes. Finally, RT-qPCR and immunohistochemical assay were used to verify the differential expression of hub genes related to prognosis. Results A total of 18 differential co-expression genes were screened out in this study, and PPI network analysis identified 10 key genes (TNFRSF11B, HOXC10, HOXA10, TEAD4, GKN2, GKN1, SALL4, SGK1, ANGPT2 and NKX6-2). The Results of survival analysis found that the high expression of HOXA10(P=0.014) and ANGPT2(P=0.002) may be related to the survival and prognosis of GC patients, and RT-qPCR and immunohistochemical assay further verified the high expression of these 2 molecules in GC tissues(P < 0.05). Conclusion HOXA10 and ANGPT2 are hub genes for prognosis of GC, and may be used as latent biomarkers of prediction.

Keywords

• bioinformatics
• gastric cancer
• prognosis
• weighted gene co-expression network analysis
• differentially co-expressed genes