LSD1 overexpression is associated with poor prognosis in basal-like breast cancer, and sensitivity to PARP inhibition

PLoS One. 2015 Feb 13;10(2):e0118002. doi: 10.1371/journal.pone.0118002. eCollection 2015.

Abstract

LSD1, a lysine-specific histone demethylase, is overexpressed in several types of cancers and linked to poor outcomes. In breast cancer, the significance of LSD1 overexpression is not clear. We have performed an in silico analysis to assess the relationship of LSD1 expression to clinical outcome. We demonstrate that LSD1 overexpression is a poor prognostic factor in breast cancer, especially in basal-like breast cancer, a subtype of breast cancer with aggressive clinical features. This link is also observed in samples of triple negative breast cancer. Interestingly, we note that overexpression of LSD1 correlates with down-regulation of BRCA1 in triple negative breast cancer. This phenomenon is also observed in in vitro models of basal-like breast cancer, and is associated with an increased sensitivity to PARP inhibitors. We propose therefore that high expression levels of the demethylase LSD1 is a potential prognostic factor of poor outcome in basal-like breast cancer, and that PARP inhibition may be a therapeutic strategy of interest in this poor prognostic subtype with overexpression of LSD1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Computational Biology / methods
  • Databases, Genetic
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Profiling
  • Gene Expression*
  • Histone Demethylases / genetics*
  • Histone Demethylases / metabolism
  • Humans
  • Immunohistochemistry
  • Neoplasms, Basal Cell / drug therapy
  • Neoplasms, Basal Cell / genetics*
  • Neoplasms, Basal Cell / mortality*
  • Neoplasms, Basal Cell / pathology
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology*
  • Prognosis
  • RNA, Messenger
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / mortality

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • RNA, Messenger
  • Histone Demethylases
  • KDM1A protein, human

Grants and funding

KS received a grant of St. Marianna University and ASS received a grant of St. Marianna University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.