The effect of androgen receptor expression on clinical characterization of metastatic breast cancer

Oncotarget. 2017 Jan 31;8(5):8693-8706. doi: 10.18632/oncotarget.14414.

Abstract

In breast cancer (BC), androgen receptor (AR) expression is related to estrogen receptor (ER) and/or progesterone receptor (PgR) expression. AR expression is an indicator of good prognosis in breast cancer regardless of hormone receptor (HR) status. In this study, we evaluated the effect of AR-related gene expression on clinical characterization of metastatic BC. We performed RNA-Seq to evaluate gene expression using mRNA extracted from 37 patients with metastatic BC. Intrinsic subtype prediction, analysis of differential gene expression, and gene set enrichment pathway analysis were then performed. Metastatic BCs were categorized into three subgroups based on AR, ER, PgR, and HER2 expression. According to this subcategorization, 70 genes including AR, ER, and HER2 were differentially expressed among the three groups. In gene set enrichment pathway analysis, the low AR group was associated with the cell cycle pathway, whereas mammalian target of rapamycin (mTOR) pathways was prevalent in the high ER and AR group. In survival analysis, a higher level of AR expression correlated with prolonged overall survival in metastatic BC (high expression vs. low expression, median OS 53.1 vs. 27.2 months, p=.001). In conclusion, we propose that AR and AR-related gene expression could be utilized to predict the prognosis of metastatic BC and thus may be useful in treatment planning for refractory BC.

Keywords: RNA-Seq; androgen receptor (AR); metastatic breast cancer; prognosis.

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cell Movement / genetics*
  • Female
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Metastasis
  • Phenotype
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • RNA, Messenger / genetics*
  • Receptor, ErbB-2 / analysis
  • Receptors, Androgen / genetics*
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Risk Factors
  • Sequence Analysis, RNA
  • Signal Transduction / genetics
  • Time Factors
  • Transcriptome

Substances

  • AR protein, human
  • Biomarkers, Tumor
  • RNA, Messenger
  • Receptors, Androgen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Receptor, ErbB-2