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The potential role of cuproptosis-related genes for therapy and immunoregulation in pan-cancer

Jianpeng Zhou1, Chuanlei Wang1, Yao Zhi1

  • 1Department of Hepatobiliary and Pancreatic Surgery I, General Surgery Center, The First Hospital of Jilin University, Changchun, Jilin Province, China.

Plos One
|July 2, 2025
PubMed

Insights

Cuproptosis regulators, like FDX1 and SLC31A1, show altered expression across many cancers, impacting patient survival and the tumor microenvironment. Understanding these genes offers new strategies for cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genomics

Background:

  • Current cancer therapies face challenges with selectivity, side effects, and resistance.
  • Trace metal element manipulation, particularly copper, is a novel therapeutic strategy.
  • Cuproptosis, a copper-induced cell death pathway, presents a potential approach for overcoming cancer resistance.

Purpose of the Study:

  • To investigate the expression patterns and clinical significance of cuproptosis-related genes (FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, SLC31A1) across various cancer types.
  • To analyze the association of these genes with tumor mutation burden, immune microenvironment, and drug sensitivity.
  • To explore the prognostic value of cuproptosis-related genes in pan-cancer analysis.

Main Methods:

  • Pan-cancer analysis of cuproptosis-related gene expression.
  • Evaluation of correlations between gene expression and tumor mutation burden (TMB).
  • Assessment of associations with immune-related scores, tumor-infiltrating immune cells, and drug sensitivity.

Main Results:

  • Significant differential expression of cuproptosis-related genes was observed across multiple cancer types.
  • Higher expression correlated with improved survival in KIRC and KIPAN cancers.
  • Gene expression showed varied associations with immune scores and specific immune cell populations (CLP, Th2, NKT, Th1).

Conclusions:

  • Cuproptosis-related genes are dysregulated in cancer and possess prognostic value.
  • These genes may play a role in modulating the tumor immune microenvironment.
  • Targeting cuproptosis offers a promising avenue for enhancing cancer treatment efficacy, especially in resistant cases.

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