Ferroptosis-related Genes for Overall Survival Prediction in Patients with Colorectal Cancer can be Inhibited by Gallic acid

Int J Biol Sci. 2021 Mar 1;17(4):942-956. doi: 10.7150/ijbs.57164. eCollection 2021.

Abstract

Colorectal cancer (CRC) is one of the most deadly malignant tumors, which seriously threatens human health. Ferroptosis, a new type of iron-dependent cell regulatory necrosis. Inducing ferroptosis of tumor cells is regarded as a potential treatment strategy. However, the prognostic value of ferroptosis-related genes in CRC remains to be further elucidated. Gallic acid, widely used in the chemical, pharmaceutical, and food fields, is a dietary supplement with potential prescription significance. In this study, the mRNA expression profiles and corresponding clinical data of CRC patients were downloaded from public databases. Gene Expression Profiling Interactive Analysis (GEPIA) was used to evaluate the expression levels of ferroptosis-related genes. In addition, bioinformatics analysis showed the prognostic value of ferroptosis-related genes in CRC. Molecular docking predicts the binding status of gallic acid and ferroptosis-related genes. The experiment confirmed the correctness of the predicted results. Our results show that in the TCGA cohort, 30 ferroptosis-related genes are differentially expressed between CRC and adjacent normal tissues. Among them, eight differentially expressed genes are related to overall survival. Gallic acid can bind to ferroptosis-related targets and regulate the expression of corresponding proteins, and ferroptosis inhibitors reversed the experimental results. In summary, eight new ferroptosis-related genes can be used to predict the prognosis of CRC. Gallic acid can improve CRC by regulating ferroptosis.

Keywords: Colorectal cancer; Ferroptosis; Gallic acid; Natural product..

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Case-Control Studies
  • Colitis, Ulcerative / drug therapy*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / prevention & control
  • Disease Models, Animal
  • Drug Screening Assays, Antitumor
  • Ferroptosis / drug effects*
  • Ferroptosis / genetics
  • Gallic Acid / pharmacology
  • Gallic Acid / therapeutic use*
  • Gene Expression Profiling
  • HCT116 Cells
  • Humans
  • Molecular Docking Simulation
  • Protein Interaction Maps
  • Rats

Substances

  • Gallic Acid