A transcriptional co-expression network-based approach to identify prognostic biomarkers in gastric carcinoma

BACKGROUND: Gastric carcinoma is a very diverse disease. The progression of gastric carcinoma is influenced by complicated gene networks. This study aims to investigate the actual and potential prognostic biomarkers related to survival in gastric carcinoma patients to further our understanding of tumor biology. METHODS: A weighted gene co-expression network analysis was performed with a transcriptome dataset to identify networks and hub genes relevant to gastric carcinoma prognosis. Data was obtained from 300 primary gastric carcinomas (GSE62254). A validation dataset (GSE34942 and GSE15459) and TCGA dataset confirmed the results. Gene ontology, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene set enrichment analysis (GSEA) were performed to identify the clusters responsible for the biological processes and pathways of this disease. RESULTS: A brown transcriptional module enriched in the organizational process of the extracellular matrix was significantly correlated with overall survival (HR = 1.586, p = 0.005, 95% CI [1.149–2.189]) and disease-free survival (HR = 1.544, p = 0.008, 95% CI [1.119–2.131]). These observations were confirmed in the validation dataset (HR = 1.664, p = 0.006, 95% CI [1.155–2.398] in overall survival). Ten hub genes were identified and confirmed in the validation dataset from this brown module; five key biomarkers (COL8A1, FRMD6, TIMP2, CNRIP1 and GPR124 (ADGRA2)) were identified for further research in microsatellite instability (MSI) and epithelial-tomesenchymal transition (MSS/EMT) gastric carcinoma molecular subtypes. A high expression of these genes indicated a poor prognosis. CONCLUSION: A transcriptional co-expression network-based approach was used to identify prognostic biomarkers in gastric carcinoma. This method may have potential for use in personalized therapies, however, large-scale randomized controlled clinical trials and replication experiments are needed before these key biomarkers can be applied clinically.