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Histone lysine demethylases in breast cancer

Elisa Paolicchi1, Francesco Crea, William L Farrar

  • 1Transgenic Oncogenesis and Genomics Section, Laboratory of Cancer Biology and Genetics, National Cancer Institute/NIH, Bethesda, MD 20892, USA.

Critical Reviews in Oncology/Hematology
|December 26, 2012
PubMed

Insights

Histone lysine demethylases (KDMs) impact breast cancer (BC) prognosis. High KDM3B and KDM5A expression correlate with better outcomes, while KDM6A overexpression indicates a poorer prognosis, suggesting KDMs as potential BC therapeutic targets.

Area of Science:

  • Epigenetics
  • Cancer Biology
  • Molecular Oncology

Background:

  • Histone lysine demethylases (KDMs) are enzymes that remove methyl groups from histones.
  • KDMs play critical roles in gene transcription, acting as oncogenes or tumor suppressors in cancer.
  • The specific role of KDMs in breast cancer (BC) requires further investigation.

Purpose of the Study:

  • To investigate the correlation between KDM expression and breast cancer prognosis.
  • To identify potential KDM biomarkers for predicting BC patient outcomes.
  • To explore KDMs as therapeutic targets for breast cancer.

Main Methods:

  • Utilized the Oncomine database to analyze KDM gene expression in breast cancer datasets.
  • Correlated KDM expression levels with clinical outcomes, including recurrence-free survival and response to therapy.
  • Examined the association between KDM expression and patient mortality.

Main Results:

  • KDM3B and KDM5A high expression is linked to better BC prognosis (no recurrence after mastectomy, p=0.005; docetaxel response, p=0.005).
  • KDM6A overexpression is associated with unfavorable BC prognosis (1-year mortality, p=8.65E-7).
  • Significant correlations were observed between specific KDM expression patterns and breast cancer patient outcomes.

Conclusions:

  • KDMs are significantly associated with breast cancer prognosis, highlighting their potential as biomarkers.
  • Specific KDMs (KDM3B, KDM5A, KDM6A) show differential correlations with patient outcomes, suggesting context-dependent roles.
  • Targeting KDMs, potentially through their interaction with Polycomb Group genes (PcG), may offer novel therapeutic strategies for breast cancer.

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