Identification of key biomarkers and potential signaling pathway associated with poor progression of gastric cancer

BACKGROUND: We aimed to identify the key differentially expressed genes (DEGs) associated with poor prognosis in gastric cancer (GC) and to elucidate the underlying molecular mechanisms in order to provide a therapeutic target for this disease. METHODS: The DEGs common in two datasets, GSE54129 and GSE79973, were screened. GO and KEGG enrichment analyses were then performed for these DEGs using DAVID’s tool. STRING and the Cytoscope software were also used to analyze the protein-protein interaction (PPI) networks of the DEGs common between the two datasets. RESULTS: A total of 164 common DEGs were identified from GSE79973 and GSE54129 datasets, 42 were up-regulated and 122 were down-regulated in GC. KEGG analysis demonstrated that up-regulated DEGs were mainly enriched for focal adhesion, ECM-receptor interaction, PI3K-Akt signaling pathway, protein digestion and absorption, and vascular smooth muscle contraction, while down-regulated DEGs were enriched for chemical carcinogenesis, metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450, and retinol metabolism (P<0.05). Obtained PPI network for the 164 DEGs via Cytotype software, using MCODE app of Cytotype software we identified 13 hub genes. Twelve of these genes were found to be associated with poor prognosis in GC by survival analysis. Post validation by the GEPIA, Oncomine, and Human Protein Atlas databases, eight genes (COL4A1, COL6A3, COL1A2, COL1A1, THBS2, COL11A1, SPP1, and FN1) were found to be up-regulated in GC tissues and correlated with poor prognosis of GC. CONCLUSIONS: COL4A1, COL6A3, COL1A2, COL1A1, THBS2, COL11A1, SPP1, and FN1 could serve as potential targets for GC diagnosis and prognosis.