Identification of the RP11-21C4.1/SVEP1 gene pair associated with FAT2 mutations as a potential biomarker in gastric cancer

Abstract

ABSTRACT Gastric cancer (GC) is one of the most common malignancies worldwide. Despite rapid advances in systemic therapy, GC remains the third leading cause of cancer-related deaths. We aimed to identify a novel prognostic signature associated with FAT2 mutations in GC. We analyzed the expression levels of FAT2-mutant and FAT2-wildtype GC samples obtained from The Cancer Genome Atlas (TCGA). The Kaplan–Meier survival curve showed that patients with FAT2 mutations showed better prognosis than those without the mutation. Sixteen long non-coding RNAs (lncRNAs) and 62 messenger RNAs (mRNAs) associated with FAT2 mutations were correlated with the prognosis of GC. We then constructed a 4-mRNA signature and a 5-lncRNA signature for GC. Finally, we identified the most relevant RP11-21 C4.1/SVEP1 gene pair as a prognostic signature of GC that exhibited superior predictive performance in comparison with the 4-mRNA or 5-lncRNA signature by weighted gene correlation network analysis (WGCNA) and Cox proportional hazards regression analysis. In this study, we constructed a prognostic signature of GC by integrative genomics analysis, which also provided insights into the molecular mechanisms linked to FAT2 mutations in GC.