Could CTSK and COL4A2 be specific biomarkers of poor prognosis for patients with gastric cancer in Asia?-a microarray analysis based on regional population.

Abstract

In the purpose of identifying reliable biomarkers for evaluating prognosis, monitoring recurrence and exploring new therapeutic targets, it is quite necessary to screen for the genetic changes and potential molecular mechanisms of the occurrence and development of gastric cancer (GC) from the aspects of race and region. Target datasets were retrieved from Gene Expression Omnibus (GEO) database with "gastric cancer" as the key word, and corresponding data was downloaded. The differentially expressed genes (DEGs) were obtained by using limma R package, and the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for DEGs were analyzed in Enirchr database. Protein-protein interaction (PPI) network and molecular module were also constructed through STRING database and Cytoscape software. Survival analyses were completed for DEGs in GEO and Kaplan-Meier plotter database via cross validation. Finally, the correlation between gene expression and the infiltration cell levels in tumor microenvironment (TME) was explored based on the tumor immune estimation resource (TIMER) database. Five GC-related microarray datasets were selected and used for differential analysis, and 222 DEGs were identified. GO analyses of DEGs were mainly involved in cell metabolism and the formation of extracellular matrix (ECM). The top enriched pathways of DEGs were protein digestion and absorption, ECM-receptor interaction, focal adhesion (FA), PI3K-Akt signaling pathway. Survival analyses of DEGs revealed that the expression levels of CTSK and COL4A2 were significantly associated with poor prognosis of GC patients in Asian. Specifically, the high expression of CTSK had a closely related to the infiltration level of inflammatory cell in TME. CTSK and COL4A2 could play a critical role in the pathogenesis of GC and act as the promising prognostic biomarkers. CTSK could induce the formation of immunosuppressive TME and promote the immune escape of GC cells.