Characterization and clinical implications of CpG island methylator phenotypes of resistant tumors

Fei Hou1, Xu Zhou1,2, Yu-E Huang3

  • 1Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China.

Clinical Epigenetics
|January 30, 2026
PubMed
Abstract

Insights

This study identifies DNA methylation subtypes in drug-resistant cancers, improving prognosis and treatment selection. These subtypes, like CR_CIMP in low-grade glioma, offer new ways to stratify patients for targeted therapies.

Area of Science:

  • Cancer Genomics
  • Epigenetics
  • Computational Biology

Background:

  • Drug resistance in cancer presents significant heterogeneity and complexity.
  • Stratifying resistant tumors is crucial for prognosis and guiding treatment.
  • DNA methylation-based subtypes of resistant tumors remain poorly characterized.

Purpose of the Study:

  • To characterize DNA methylation subtypes in various drug-resistant tumors.
  • To identify novel molecular subgroups for improved cancer patient stratification.
  • To explore potential therapeutic strategies based on identified subtypes.

Main Methods:

  • Retrieved DNA methylation profiles from public databases (TCGA, GEO).
  • Applied consensus clustering on variable CpGs to identify methylation subtypes.
  • Utilized random forest models for subtype prediction in specific cancers.

Main Results:

  • Identified two DNA methylation subtypes (CR_CIMP+ and CR_CIMP-) in Temozolomide-resistant low-grade glioma.
  • The CR_CIMP- subtype showed poorer prognosis, reduced drug response, and activated resistance pathways.
  • Discovered distinct CR_CIMP subtypes in Gemcitabine-resistant pancreatic cancer/bladder cancer and anti-PD1/PD-L1-resistant NSCLC.

Conclusions:

  • Uncovered novel DNA methylation subtypes within drug-resistant tumors.
  • Enables more precise stratification of resistant tumors for clinical decision-making.
  • Provides a foundation for personalized therapy selection in resistant cancers.

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