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

Frontiers in Oncology

Ruochen Liu¹  Guanghui Zhang¹  Chaowei Deng¹  Sicheng Wan¹  Zhen Dong¹  Jianbing Hou¹  Xiaodong Lai²  Ruoyue Tan³  Hongjuan Cui³ 

[1] Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, Chongqing, China;Department of Critical Care Medicine, The Thirteenth People’s Hospital of Chongqing, Chongqing, China;NHC Key Laboratory of Birth Defects and Reproductive Health (Chongqing Key Laboratory of Birth Defects and Reproductive Health, Chongqing Population and Family Planning Science and Technology Research Institute), Chongqing, China;State Key Laboratory of Silkworm Genome Biology, Institute of Sericulture and Systems Biology, College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing, China;

关键词: stomach adenocarcinoma (STAD);    WGCNA;    early diagnosis;    TCGA;    biomarkers;    prognosis;   

DOI  :  10.3389/fonc.2021.636461

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown