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

Bioengineered. 2021 Dec;12(1):4361-4373. doi: 10.1080/21655979.2021.1953211.

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.

Keywords: RP11-21C4.1; SVEP1; gastric cancer; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Cadherins / genetics*
  • Cell Adhesion Molecules / genetics*
  • Humans
  • Mutation / genetics
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Transcriptome / genetics

Substances

  • Biomarkers, Tumor
  • Cadherins
  • Cell Adhesion Molecules
  • FAT2 protein, human
  • RNA, Long Noncoding
  • SVEP1 protein, human

Grants and funding

This work was supported by the National Natural Science Foundation of China [grant number 81960430] and Hospital fund project of the first hospital of Lanzhou university [grant number ldyyyn2018-38].