Abstract
Gastric adenocarcinoma (GAC), also known as stomach adenocarcinoma (STAD), is one of the most lethal malignancies in the world. It is vital to classify and detect the hub genes and key pathways participated in the initiation and progression of GAC. In this study, we collected and sequenced 15 pairs of GAC tumor tissues and the adjacent normal tissues. Differentially expressed genes (DEGs) were analyzed and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis were used to annotate the unique biological significance and important pathways of enriched DEGs. Moreover, we constructed the protein-protein interaction (PPI) network by Cytoscape and conducted KEGG enrichment analysis of the prime module. We further applied the TCGA database to start the survival analysis of these hub genes by Kaplan-Meier estimates. Finally, we obtained total 233 DEGs consisted of 64 up-regulated genes and 169 down-regulated genes. GO enrichment analysis found that DEGs most significantly enriched in single organism process, extracellular region, and extracellular region part. KEGG pathway enrichment analysis suggested that DEGs most significantly enriched in Protein digestion and absorption, Gastric acid secretion, and ECM-receptor interaction. Furthermore, the PPI network showed that the top 10 hub genes in GAC were IL8, COL1A1, MMP9, SST, COL1A2, TIMP1, FN1, SPARC, ALDH1A1, and SERPINE1 respectively. The prime gene interaction module in PPI network was enriched in protein digestion and absorption, ECM receptor interaction, the PI3K-Akt signaling pathway, and pathway in cancer. Survival analysis based on the TCGA database found that the expression of the FN1, SERPINE1, and SPARC significantly predicted poor prognosis of GAC. Collectively, we identified several hub genes and key pathways associated with GAC initiation and progression by analyzing the microarray data on DEGs, which provided a detailed molecular mechanism underlying GAC occurrence and progression.
Highlights
Gastric cancers are the fifth commonest cancer after lung, breast, colorectal and prostate cancers[1]
We identified a set of hub genes that participated in several cancer-relevant pathways and their abnormal expression are correlated with the clinical prognosis of Gastric adenocarcinoma (GAC) people by overall survival analysis
Total 15 pairs of GAC tumor and normal samples were analyzed (Fig. 1A) and the basic global gene expression pattern among all samples was denoted by Pearson correlation matrix for calculation of pairwise correlation coefficient (Fig. 1B)
Summary
Gastric cancers are the fifth commonest cancer after lung, breast, colorectal and prostate cancers[1]. It imposes a considerable health burden worldwide. Microarray could be used to probe the key biomarkers and provide a better understanding of the molecular mechanisms involved in GAC. Exploring novel and effective molecular biomarkers to elucidate effective therapeutic targets for GAC patients is still imperative. To discover the hub genes and key pathways associated with the initiation and progression of GAC, we applied differential gene expression analysis and functional enrichment analysis. We identified a set of hub genes that participated in several cancer-relevant pathways and their abnormal expression are correlated with the clinical prognosis of GAC people by overall survival analysis
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