mRNA ratios of AR to ESR1 and PGR distinguish breast cancer subtypes based on public datasets and experimental models

TL;DR

This study shows that the ratio of androgen receptor to estrogen and progesterone receptor mRNA levels can help identify more aggressive breast cancer subtypes.

Contribution

The study introduces AR/ESR1 and AR/PGR mRNA ratios as potential biomarkers for distinguishing aggressive breast cancer subtypes.

Findings

Higher AR/ESR1 and AR/PGR ratios were linked to Luminal B and HER2-enriched breast cancer subtypes.

Positive AR/ESR1 and AR/PGR ratios were observed in ER-negative cell lines and patient tumors.

These ratios may indicate more aggressive breast cancer with worse prognosis.

Abstract

The role of the androgen receptor (AR) in breast cancer (BC) remains incompletely understood. Here, we conducted a meta-analysis of large-scale microarray transcriptomic datasets to evaluate whether the mRNA expression levels of the androgen receptor gene, relative to those of the estrogen receptor gene (AR/ESR1 ratio) and the progesterone receptor gene (AR/PGR ratio), can help differentiate BC tumor subtypes. Additionally, we used qRT-PCR assays to assess the mRNA levels of the AR/ESR1 and AR/PGR ratios in four cell lines representative of different BC subtypes (MCF7, BT474, MDA-MB453, and MDA-MB231), as well as in breast tissue from a small group of patients (11 cases) stratified by estrogen receptor (ER) status. Our results showed that higher AR gene expression relative to ESR1 and PGR (≥ 2.0 and ≥ 1.54, respectively) were associated with BC patients classified under the Luminal B and HER2-enriched subtypes. Positive values of AR/ESR1 and AR/PGR ratios were also observed in the ER-negative (ER-) cell line MDA-MB453, as well as in tumor tissue from ER- BC patients. Our findings confirm that higher or even positive AR/ESR1 and AR/PGR ratios may be associated with BC cases exhibiting more aggressive clinical and biological features, leading to a worse prognosis.

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