Experimentally validated oxidative stress -associated prognostic signatures describe the immune landscape and predict the drug response and prognosis of SKCM

Front Immunol. 2024 Apr 10:15:1387316. doi: 10.3389/fimmu.2024.1387316. eCollection 2024.

Abstract

Background: Skin Cutaneous Melanoma (SKCM) incidence is continually increasing, with chemotherapy and immunotherapy being among the most common cancer treatment modalities. This study aims to identify novel biomarkers for chemotherapy and immunotherapy response in SKCM and explore their association with oxidative stress.

Methods: Utilizing TCGA-SKCM RNA-seq data, we employed Weighted Gene Co-expression Network Analysis (WGCNA) and Protein-Protein Interaction (PPI) networks to identify six core genes. Gene co-expression analysis and immune-related analysis were conducted, and specific markers associated with oxidative stress were identified using Gene Set Variation Analysis (GSVA). Single-cell analysis revealed the expression patterns of Oxidative Stress-Associated Genes (OSAG) in the tumor microenvironment. TIDE analysis was employed to explore the association between immune therapy response and OSAG, while CIBERSORT was used to analyze the tumor immune microenvironment. The BEST database demonstrated the impact of the Oxidative Stress signaling pathway on chemotherapy drug resistance. Immunohistochemical staining and ROC curve evaluation were performed to assess the protein expression levels of core genes in SKCM and normal samples, with survival analysis utilized to determine their diagnostic value.

Results: We identified six central genes associated with SKCM metastasis, among which the expression of DSC2 and DSC3 involved in the oxidative stress pathway was closely related to immune cell infiltration. DSC2 influenced drug resistance in SKMC patients. Furthermore, downregulation of DSC2 and DSC3 expression enhanced the response of SKCM patients to immunotherapy.

Conclusion: This study identified two Oxidative Stress-Associated genes as novel biomarkers for SKCM. Additionally, targeting the oxidative stress pathway may serve as a new strategy in clinical practice to enhance SKCM chemotherapy and sensitivity.

Keywords: SKCM; drug resistance; immune; immunotherapy response; oxidative stress network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor*
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Immunotherapy / methods
  • Male
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Melanoma* / immunology
  • Melanoma* / metabolism
  • Melanoma, Cutaneous Malignant
  • Middle Aged
  • Oxidative Stress*
  • Prognosis
  • Protein Interaction Maps
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / immunology
  • Skin Neoplasms* / mortality
  • Transcriptome
  • Tumor Microenvironment* / immunology

Substances

  • Biomarkers, Tumor

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Basic research of Guizhou Cooperational Science Foundation [number ZK (2021) general 466] and Science and Technology Fund of Guizhou Provincial Health Commission [number gzwkj2022-062].