Related Experiment Video

Updated: May 28, 2026

Predictive Immune Modeling of Solid Tumors
08:50

Predictive Immune Modeling of Solid Tumors

Published on: February 25, 2020

EZH2-Associated Hypermethylated Gene Signature Predicts Immunotherapy Response and Implicates DUSP5 in Tumor-Immune

Mingzhan Xue1, Sujitha Jeya1, Reem Elasad1

  • 1Translational Oncology Research Centre, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Doha P.O. Box 34110, Qatar.

Cancers
|May 27, 2026
PubMed

Insights

This study identifies an epigenetic signature in triple-negative breast cancer (TNBC) linked to immune evasion. The Dual Specificity Phosphatase 5 (DUSP5) gene may predict immunotherapy response in TNBC patients.

Area of Science:

  • Oncology
  • Epigenetics
  • Immunotherapy

Background:

  • Triple-negative breast cancer (TNBC) is a target for immune checkpoint blockade, but biomarkers for treatment response are lacking.
  • Enhancer of Zeste Homolog 2 (EZH2)-mediated repression contributes to immune evasion, but its role in TNBC immunity and outcomes is unclear.

Purpose of the Study:

  • Identify EZH2-repressed genes in TNBC.
  • Evaluate their role in anti-tumor immunity and as predictors of immunotherapy response.

Main Methods:

  • In silico analysis of TCGA breast cancer cohorts to find EZH2-associated hypermethylated genes.
  • Defined a 30-gene signature (30GS) based on repression and hypermethylation.
  • Validated associations with outcomes and immunotherapy response in I-SPY2 and independent TNBC cohorts.

Main Results:

  • The 30GS was reduced in TNBC and associated with better outcomes and immune signatures.
  • The 30GS predicted pathological complete response to chemo-immunotherapy in the I-SPY2 cohort (AUC=0.7377).
  • Dual Specificity Phosphatase 5 (DUSP5) was strongly linked to immune parameters; high DUSP5 correlated with immune-related pathways in TNBC.

Conclusions:

  • An EZH2-associated epigenetic program influences tumor-intrinsic immunity in TNBC.
  • DUSP5 is a potential biomarker for immune-related transcriptional states and immunotherapy response in TNBC.
Keywords:
DNA methylationDUSP5EZH2MAPK signalingTriple-Negative Breast Cancerbiomarkerimmune regulationimmunotherapy

More Related Videos

Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker07:47

Multiomics Analysis of TMEM200A as a Pan-Cancer Biomarker

Published on: September 15, 2023

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...