Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer

Sci Rep. 2020 Dec 18;10(1):22292. doi: 10.1038/s41598-020-79248-4.

Abstract

New therapies are an urgent medical need in all breast cancer subgroups. Metabotropic glutamate receptor 1 (mGluR1) is suggested as a potential new molecular target. We examined the prevalence mGluR1 expression in different clinically relevant breast cancer subgroups and determined its association with prognosis. In this retrospective cohort, 394 consecutive primary breast cancer tissues were incorporated into a tissue microarray and immunohistochemically stained for mGluR1. The prevalence of mGluR1 protein expression in different breast cancer subgroups was evaluated and correlated with metastasis-free survival (MFS) and overall survival (OS). In total, 56% (n = 219) breast cancer tissues had mGluR1 expression. In estrogen receptor (ER)-negative tumors, 31% (n = 18/58) had mGluR1 expression that was significantly associated with MFS (HR 5.00, 95% CI 1.03-24.35, p = 0.046) in multivariate analysis, independently from other prognostic factors. Of the 44 triple-negative breast cancer (TNBC), 25% (n = 11) expressed mGluR1. mGluR1 expression in TNBC was significantly associated with shorter MFS (HR 8.60, 95% CI 1.06-20.39, p = 0.044) and with poor OS (HR 16.07, 95% CI 1.16-223.10, p = 0.039). In conclusion, mGluR1 is frequently expressed in breast cancer. In ER-negative breast cancer and in TNBC mGluR1 protein expression is an unfavorable prognostic marker. This study provides rationale to explore mGluR1 as a novel target for breast cancer treatment, especially for the more aggressive TNBC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Middle Aged
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / genetics*
  • Receptors, Metabotropic Glutamate / genetics*
  • Retrospective Studies
  • Triple Negative Breast Neoplasms / epidemiology
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor type 1
  • ERBB2 protein, human
  • Receptor, ErbB-2