Tetraspanin family identified as the central genes detected in gastric cancer using bioinformatics analysis

Abstract

Gastric cancer has become a serious disease in the past decade. It has the second highest mortality rate among the four most common cancer types, leading to ~700,000 mortalities annually. Previous studies have attempted to elucidate the underlying biological mechanisms of gastric cancer. The present study aimed to obtain useful biomarkers and to improve the understanding of gastric cancer mechanisms at the genetic level. The present study used bioinformatics analysis to identify 1,829 differentially expressed genes (DEGs) which were obtained from the GSE54129 dataset. Using protein-protein interaction information from the Search Tool for the Retrieval of Interacting Genes database, disease modules were constructed for gastric cancer using Cytoscape software. In the Gene Ontology analysis of biology processes, upregulated genes were significantly enriched in ‘extracellular matrix organization’, ‘cell adhesion’ and ‘inflammatory response’, whereas downregulated DEGs were significantly enriched in ‘xenobiotic metabolic process’, ‘oxidation-reduction process’ and ‘steroid metabolic process’. During Kyoto Encyclopedia of Genes and Genomes analysis, upregulated DEGs were significantly enriched in ‘extracellular matrix-receptor interaction’, ‘focal adhesion’ and ‘PI3K-Akt signaling pathway’, whereas the downregulated DEGs were significantly enriched in ‘chemical carcinogenesis’, ‘metabolism of xenobiotics by cytochrome P450’ and ‘peroxisome’. The present study additionally identified 10 hub genes from the DEGs: Tumor protein p53 (TP53), C-X-C motif chemokine ligand 8 (CXCL8), tetraspanin 4 (TSPAN4), lysophosphatidic acid receptor 2 (LPAR2), adenylate cyclase 3 (ADCY3), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), neuromedin U (NMU), C-X-C motif chemokine ligand (CXCL12), fos proto-oncogene, AP-1 transcription factor subunit (FOS) and sphingosine-1-phosphate receptor 1 (S1PR1), which have high degrees with other DEGs. The survival analysis revealed that the high expression of ADCY3, LPAR2, S1PR1, TP53 and TSPAN4 was associated with a lower survival rate, whereas high expression of CXCL8, FOS, NMU and PIK3R1 was associated with a higher survival rate. No significant association was identified between CXCL12 and survival rate. Additionally, TSPAN1 and TSPAN8 appeared in the top 100 DEGs. Finally, it was observed that 4 hub genes were highly expressed in gastric cancer tissue compared with para-carcinoma tissue in the 12 patients; the increased TSPAN4 was significant (>5-fold). Tetraspanin family genes may be novel biomarkers of gastric cancer. The findings of the present study may improve the understanding of the molecular mechanisms underlying the development of gastric cancer.