Identification of Early Diagnostic and Prognostic Biomarkers via WGCNA in Stomach Adenocarcinoma

Stomach adenocarcinoma (STAD) is a leading cause of cancer deaths, and the outcome of the patients remains dismal for the lack of effective biomarkers of early detection. Recent studies have elucidated the landscape of genomic alterations of gastric cancer and reveal some biomarkers of advanced-stage gastric cancer, however, information about early-stage biomarkers is limited. Here, we adopt Weighted Gene Co-expression Network Analysis (WGCNA) to screen potential biomarkers for early-stage STAD using RNA-Seq and clinical data from TCGA database. We find six gene clusters (or modules) are significantly correlated with the stage-I STADs. Among these, five hub genes, i.e., MS4A1, THBS2, VCAN, PDGFRB, and KCNA3 are identified and significantly de-regulated in the stage-I STADs compared with the normal stomach gland tissues, which suggests they can serve as potential early diagnostic biomarkers. Moreover, we show that high expression of VCAN and PDGFRB is associated with poor prognosis of STAD. VCAN encodes a large chondroitin sulfate proteoglycan that is the main component of the extracellular matrix, and PDGFRB encodes a cell surface tyrosine kinase receptor for members of the platelet-derived growth factor (PDGF) family. Consistently, Gene Ontology (GO) analysis of differentially expressed genes in the STADs indicates terms associated with extracellular matrix and receptor ligand activity are significantly enriched. Protein-protein network interaction analysis (PPI) and Gene Set Enrichment Analysis (GSEA) further support the core role of VCAN and PDGFRB in the tumorigenesis. Collectively, our study identifies the potential biomarkers for early detection and prognosis of STAD.

Automated summary

This study identified potential biomarkers for early detection and prognosis of stomach adenocarcinoma (STAD) using Weighted Gene Co-expression Network Analysis (WGCNA) on RNA-Seq and clinical data from TCGA database. Five hub genes including MS4A1, THBS2, VCAN, PDGFRB, and KCNA3 were significantly dysregulated in stage-I STADs compared to normal stomach gland tissues, suggesting their potential as early diagnostic biomarkers. High expression of VCAN and PDGFRB were associated with poor prognosis of STAD, with Gene Ontology analysis indicating terms related to extracellular matrix and receptor ligand activity being significantly enriched in differentially expressed genes in STAD. Protein-protein network interaction analysis and Gene Set Enrichment Analysis further supported the key role of VCAN and PDGFRB in tumorigenesis.