Application of RNAi-induced gene expression profiles for prognostic prediction in breast cancer

Genome Med. 2016 Oct 27;8(1):114. doi: 10.1186/s13073-016-0363-3.

Abstract

Homologous recombination (HR) is the primary pathway for repairing double-strand DNA breaks implicating in the development of cancer. RNAi-based knockdowns of BRCA1 and RAD51 in this pathway have been performed to investigate the resulting transcriptomic profiles. Here we propose a computational framework to utilize these profiles to calculate a score, named RNA-Interference derived Proliferation Score (RIPS), which reflects cell proliferation ability in individual breast tumors. RIPS is predictive of breast cancer classes, prognosis, genome instability, and neoadjuvant chemosensitivity. This framework directly translates the readout of knockdown experiments into potential clinical applications and generates a robust biomarker in breast cancer.

Keywords: Cancer prognosis; Cell proliferation; Gene knockdown profiles; Genomic instability; Homologous recombination pathway; Neoadjuvant chemotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics*
  • Computational Biology / methods
  • DNA Breaks, Double-Stranded
  • DNA Repair
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genomic Instability
  • Humans
  • Kaplan-Meier Estimate
  • Neoadjuvant Therapy
  • Outcome Assessment, Health Care / methods
  • Outcome Assessment, Health Care / statistics & numerical data
  • Prognosis
  • Proportional Hazards Models
  • RNA Interference*
  • Rad51 Recombinase / genetics
  • Transcriptome / genetics*

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Rad51 Recombinase