Development and validation of a ferroptosis-related lncRNAs prognosis signature in colon cancer

Bosn J Basic Med Sci. 2021 Oct 1;21(5):569-576. doi: 10.17305/bjbms.2020.5617.

Abstract

Ferroptosis is a form of iron-dependent programmed cell death. Regulation of ferroptosis in tumor cells is a novel treatment modality. The present study aimed to investigate ferroptosis-related long non-coding RNAs (lncRNAs) and construct a prognostic model for colon adenocarcinoma (COAD). RNA- sequencing data and ferroptosis-related genes were obtained from The Cancer Genome Atlas database and FerrDb database. COAD patients were randomly assigned to training- and validation groups. The Least Absolute Shrinkage and Selection Operator regression and Cox regression model were used to determine and develop a predictive model. The model was corroborated using the validation group and the entire group. In total, 259 ferroptosis-related genes and 905 ferroptosis-related LncRNAs were obtained. Cox model revealed and constructed seven ferroptosis-related LncRNAs signature (LINC01503, AC004687.1, AC010973.2, AP001189.3, ARRDC1-AS1, OIP5-AS1, and NCK1-DT). Patients were assigned into two groups according to the median risk score. Kaplan-Meier survival curves showed that overall survival between high- and low-risk groups was statistically significant (P<0.01). Cox multivariate analysis seven ferroptosis-related LncRNAs signature was an independent risk factor for COAD outcomes (P<0.05). The relationship between seven ferroptosis-related LncRNAs and clinicopathological features was also examined. The principal component analysis showed a difference between high- and low-risk groups intuitively. With the aid of gene set enrichment analysis, the underlying mechanisms of seven ferroptosis-related LncRNAs were uncovered, including the MAPK signaling pathway, mTOR signaling pathway, and glutathione metabolism pathway. Finally, we established and validated seven ferroptosis-related lncRNAs signature for COAD patients to predict survival. These results may provide meaningful targets for future study.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics*
  • Aged
  • Biomarkers, Tumor / analysis
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / genetics*
  • Female
  • Ferroptosis*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, Neoplasm
  • Genome, Human
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Principal Component Analysis
  • Prognosis
  • Proportional Hazards Models
  • RNA, Long Noncoding / genetics*
  • Risk
  • Risk Assessment
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • TOR Serine-Threonine Kinases