Identification of Significant Genes with Peritoneal Metastasis After Gastric Cancer Surgery via Bioinformatical Analysis

Abstract

Background: Peritoneal metastasis (PM) is the most prevalent recurrence after gastric cancer (GC) surgery, which is also the leading cause of GC related death. The purpose of this study is to identify significant pathways and genes associated with PM through RNA-seq and discover the potential biomarker for postoperative. Methods: Gene expression profiles were obtained from public genetic databases. 257 primary independent GC specimens (42 PM and 215 non-PM after GC surgery) were obtained in the GSE62254 dataset. Differentially expressed genes (DEGs), Kyoto Encyclopedia of Genes and Genomes (KEGG), REACTOME, Gene Ontology (GO) terms, gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) are managed with R packages. The Search Tool for the Retrieval of Interacting Genes (STRING) and the Molecular Complex Detection (MCODE) plugin was utilized in protein-protein interaction. The univariates/multivariates Cox regression and Kaplan-Meier (KM) method were used for survival analysis in the cohort from multiple public databases. Findings: We reconfirmed that PM is an independent prognostic factor in GC. Furthermore, we found that patients with PM after GC surgery showed the mesenchymal-subtype RNA signature. Three significantly downregulated pathways (REACTOME-cell cycle, REACTOME-mitotic prometaphase, and REACTOME-cell cycle mitotic) and five essential genes (BUB1, CHEK1, CENPN, NUF2, and NCAPH) were significantly correlated with PM. Interpretation: Expression of BUB1, CHEK1, CENPN, NUF2, and NCAPH are new biomarkers for postoperative PM in GC patients. Furthermore, these genes can be used as clinical predictive molecules for the risk prediction of PM patients. Funding Statement: The study was funded by the Joint Funds for the innovation of science and technology, Fujian province (13YZ0201), and Fujian Medical University Qihang Foundation (2018QH1035). Declaration of Interests: The authors declare no competing interests. Ethics Statement: Not required.