A four-DNA methylation biomarker is a superior predictor of survival of patients with cutaneous melanoma

Elife. 2019 Jun 6:8:e44310. doi: 10.7554/eLife.44310.

Abstract

Cutaneous melanoma (CM) is a life-threatening form of skin cancer. Prognostic biomarkers can reliably stratify patients at initial melanoma diagnosis according to risk, and may inform clinical decisions. Here, we performed a retrospective, cohort-based study analyzing genome-wide DNA methylation of 461 patients with CM from the TCGA database. Cox regression analyses were conducted to establish a four-DNA methylation signature that was significantly associated with the overall survival (OS) of patients with CM, and that was validated in an independent cohort. Corresponding Kaplan-Meier analysis displayed a distinct separation in OS. The ROC analysis confirmed that the predictive signature performed well. Notably, this signature exhibited much higher predictive accuracy in comparison with known biomarkers. This signature was significantly correlated with immune checkpoint blockade (ICB) immunotherapy-related signatures, and may have potential as a guide for measures of responsiveness to ICB immunotherapy.

Keywords: DNA methylation; cancer biology; cutaneous melanoma; human; immune-checkpoint blockade; prognostic biomarker; risk stratification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • DNA Methylation / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / epidemiology
  • Melanoma / genetics*
  • Melanoma / pathology
  • Melanoma, Cutaneous Malignant
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Skin Neoplasms / epidemiology
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology
  • Transcriptome / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor

Associated data

  • GEO/GSE51547