Ferroptosis-related gene CHAC1 is a valid indicator for the poor prognosis of kidney renal clear cell carcinoma

J Cell Mol Med. 2021 Apr;25(7):3610-3621. doi: 10.1111/jcmm.16458. Epub 2021 Mar 16.

Abstract

To evaluate the validity of CHAC1 for predicting the prognosis of kidney renal clear cell carcinoma (KIRC) and to explore its therapeutic potential for KIRC, we conducted several bioinformatic analyses using the sequencing data and clinical information derived from online databases. We found CHAC1 is down-regulated in KIRC samples when compared with normal samples but up-regulated in KIRC samples with relatively higher malignancy and later stages. Univariate cox analysis and multivariate cox regression analysis were conducted and the results revealed up-regulated CHAC1 is an independent risk factor for poor prognosis of KIRC. Further, the nomogram model based on the result of multivariate cox regression analysis was constructed and effectively predicted patients' 1-year, 3-year and 5-year survival respectively. The correlation analyses showed CHAC1 is associated with the immune pathway markers of memory B cell, natural killer cell and type1 T helper cell as well as the checkpoint genes like ADORA2A, CD200, CD44, CD70, HHLA2, NRP1, PDCD1LG2 and TNFRSF18. Furthermore, experiments in vitro indicated CHAC1 could induce cell death in KIRC cell lines but had limited influence on cell migration and cell invasion. In conclusion, CHAC1 is found a valid indicator for poor prognosis of kidney renal clear cell carcinoma.

Keywords: CHAC1; ferroptosis; glutathione; kidney renal clear cell carcinoma; prognosis.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinogenesis / metabolism
  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / immunology
  • Carcinoma, Renal Cell / physiopathology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Down-Regulation
  • Ferroptosis
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / immunology
  • Kidney Neoplasms / physiopathology*
  • Multivariate Analysis
  • Nomograms
  • Prognosis
  • Risk Factors
  • Survival Analysis
  • Up-Regulation
  • gamma-Glutamylcyclotransferase / pharmacology
  • gamma-Glutamylcyclotransferase / physiology*

Substances

  • Biomarkers, Tumor
  • CHAC1 protein, human
  • gamma-Glutamylcyclotransferase