Integrated analysis of a ceRNA network reveals potential prognostic lncRNAs in gastric cancer

Cancer Med. 2020 Mar;9(5):1798-1817. doi: 10.1002/cam4.2760. Epub 2020 Jan 10.

Abstract

Long noncoding RNAs (lncRNAs) have important biological functions as competing endogenous RNAs (ceRNAs) in tumors, yet the functions and regulatory mechanisms of lncRNA-related ceRNAs in gastric cancer have not been fully elucidated. In this study, we constructed a lncRNA-miRNA-mRNA ceRNA network and identified potential lncRNA biomarkers in gastric cancer. Basing on the RNA profiles downloaded from The Cancer Genome Atlas (TCGA) platform, the gastric cancer-specific differentially expressed lncRNAs, miRNAs, and mRNAs were screened for constructing a ceRNA network using bioinformatic tools. The enrichment analysis of the biological processes in Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathways was performed on the ceRNA-related DEmRNAs. According to the modularization of protein-protein interaction (PPI) network, we extracted a ceRNA subnetwork and analyzed the correlation between the expression of the lncRNAs involved and specific clinical features of patients. Next, the expression of highly up-regulated in liver cancer (HULC) and RP11-314B1.2 showed significant changes in several pathological processes involved in gastric cancer, and nine lncRNAs were found to be correlated with the overall survival of patients with gastric cancer. Through the univariate and multivariate Cox regression analyses, two lncRNAs (LINC00106 and RP11-999E24.3) were identified and utilized to establish a risk score model for assessing the prognosis of patients. The analysis results were also partially verified using quantitative real-time PCR. The findings from this study indicate that HULC, RP11-314B1.2, LINC00106, and RP11-999E24.3 could be considered as potential therapeutic targets or prognostic biomarkers in gastric cancer, and provide a new perspective for cancer pathogenesis research.

Keywords: biomarkers; ceRNA network; gastric cancer; long noncoding RNA; risk score.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Computational Biology
  • Datasets as Topic
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / metabolism
  • Middle Aged
  • Prognosis
  • Protein Interaction Maps / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / metabolism
  • RNA-Seq
  • Stomach / pathology
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / mortality*
  • Stomach Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger