Association of androgen receptor expression with glucose metabolic features in triple-negative breast cancer

PLoS One. 2022 Sep 30;17(9):e0275279. doi: 10.1371/journal.pone.0275279. eCollection 2022.

Abstract

Background: Androgen receptor (AR) is a potential therapeutic target in triple-negative breast cancer (TNBC). We aimed to elucidate the association of AR expression with glucose metabolic features in TNBC.

Methods: Two independent datasets were analyzed: FDG PET data of our institution and a public dataset of GSE135565. In PET analysis, patients with TNBC who underwent pretreatment PET between Jan 2013 and Dec 2017 were retrospectively enrolled. Clinicopathologic features and maximum standardized uptake value (SUVmax) of tumors were compared with AR expression. In GSE135565 dataset, glycolysis score was calculated by the pattern of glycolysis-related genes, and of which association with SUVmax and AR gene expression were analyzed.

Results: A total of 608 female patients were included in the PET data of our institution. SUVmax was lower in AR-positive tumors (P < 0.001) and correlated with lower AR expression (rho = -0.26, P < 0.001). In multivariate analysis, AR was a deterministic factor for low SUVmax (P = 0.012), along with other key clinicopathologic features. In the GSE135565 dataset, AR expression also exhibited a negative correlation with SUVmax (r = -0.34, P = 0.001) and the glycolysis score (r = -0.27, P = 0.013).

Conclusions: Low glucose metabolism is a signature of AR expression in TNBC. It is suggested that evaluation of AR expression status needs to be considered in clinical practice particularly in TNBC with low glucose metabolism.

MeSH terms

  • Androgens
  • Female
  • Fluorodeoxyglucose F18 / therapeutic use
  • Gene Expression
  • Glucose / therapeutic use
  • Humans
  • Prognosis
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Retrospective Studies
  • Triple Negative Breast Neoplasms* / metabolism

Substances

  • AR protein, human
  • Androgens
  • Receptors, Androgen
  • Fluorodeoxyglucose F18
  • Glucose

Grants and funding

This research was supported the Korea Health Technology R&D Project through Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea in the form of a grant (HI14C1277) awarded to JCP. This study was also funded by Chung-Ang University in the form of 2022 research grants awarded to RL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.