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Contribution of Immune Cells to Glucocorticoid Receptor Expression in Breast Cancer
Breast cancer (BC) patients experience increased stress with elevated cortisol levels, increasing risk of cancer recurrence. Cortisol binds to a cytoplasmic receptor, glucocorticoid receptor (GR) encoded by GR gene (NR3C1). We hypothesized that not only cancer cells, but even immune cells in the tum...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370149/ https://www.ncbi.nlm.nih.gov/pubmed/32629782 http://dx.doi.org/10.3390/ijms21134635 |
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author | Gandhi, Shipra Elkhanany, Ahmed Oshi, Masanori Dai, Tao Opyrchal, Mateusz Mohammadpour, Hemn Repasky, Elizabeth A. Takabe, Kazuaki |
author_facet | Gandhi, Shipra Elkhanany, Ahmed Oshi, Masanori Dai, Tao Opyrchal, Mateusz Mohammadpour, Hemn Repasky, Elizabeth A. Takabe, Kazuaki |
author_sort | Gandhi, Shipra |
collection | PubMed |
description | Breast cancer (BC) patients experience increased stress with elevated cortisol levels, increasing risk of cancer recurrence. Cortisol binds to a cytoplasmic receptor, glucocorticoid receptor (GR) encoded by GR gene (NR3C1). We hypothesized that not only cancer cells, but even immune cells in the tumor microenvironment (TME) may contribute to GR expression in bulk tumor and influence prognosis. To test this, mRNA expression data was accessed from METABRIC and TCGA. “High” and “low” expression was based on highest and lowest quartiles of NR3C1 gene expression, respectively. Single-cell sequencing data were obtained from GSE75688 and GSE114725 cohorts. Computer algorithms CIBERSORT, Gene Set Enrichment Analysis and TIMER were used. GR-high BC has better median disease-free and disease-specific survival. Single cell sequencing data showed higher GR expression on immune cells compared to cancer and stromal cells. Positive correlation between GR-high BC and CD8(+) T-cells was noted. In GR-high tumors, higher cytolytic activity (CYT) with decreased T-regulatory and T-follicular helper cells was observed. High GR expression was associated with lower proliferation index Ki67, enriched in IL-2_STAT5, apoptosis, KRAS, TGF-β signaling, and epithelial-to-mesenchymal transition. Immune cells significantly contribute to GR expression of bulk BC. GR-high BC has a favorable TME with higher CYT with favorable outcomes. |
format | Online Article Text |
id | pubmed-7370149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73701492020-07-21 Contribution of Immune Cells to Glucocorticoid Receptor Expression in Breast Cancer Gandhi, Shipra Elkhanany, Ahmed Oshi, Masanori Dai, Tao Opyrchal, Mateusz Mohammadpour, Hemn Repasky, Elizabeth A. Takabe, Kazuaki Int J Mol Sci Article Breast cancer (BC) patients experience increased stress with elevated cortisol levels, increasing risk of cancer recurrence. Cortisol binds to a cytoplasmic receptor, glucocorticoid receptor (GR) encoded by GR gene (NR3C1). We hypothesized that not only cancer cells, but even immune cells in the tumor microenvironment (TME) may contribute to GR expression in bulk tumor and influence prognosis. To test this, mRNA expression data was accessed from METABRIC and TCGA. “High” and “low” expression was based on highest and lowest quartiles of NR3C1 gene expression, respectively. Single-cell sequencing data were obtained from GSE75688 and GSE114725 cohorts. Computer algorithms CIBERSORT, Gene Set Enrichment Analysis and TIMER were used. GR-high BC has better median disease-free and disease-specific survival. Single cell sequencing data showed higher GR expression on immune cells compared to cancer and stromal cells. Positive correlation between GR-high BC and CD8(+) T-cells was noted. In GR-high tumors, higher cytolytic activity (CYT) with decreased T-regulatory and T-follicular helper cells was observed. High GR expression was associated with lower proliferation index Ki67, enriched in IL-2_STAT5, apoptosis, KRAS, TGF-β signaling, and epithelial-to-mesenchymal transition. Immune cells significantly contribute to GR expression of bulk BC. GR-high BC has a favorable TME with higher CYT with favorable outcomes. MDPI 2020-06-30 /pmc/articles/PMC7370149/ /pubmed/32629782 http://dx.doi.org/10.3390/ijms21134635 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gandhi, Shipra Elkhanany, Ahmed Oshi, Masanori Dai, Tao Opyrchal, Mateusz Mohammadpour, Hemn Repasky, Elizabeth A. Takabe, Kazuaki Contribution of Immune Cells to Glucocorticoid Receptor Expression in Breast Cancer |
title | Contribution of Immune Cells to Glucocorticoid Receptor Expression in Breast Cancer |
title_full | Contribution of Immune Cells to Glucocorticoid Receptor Expression in Breast Cancer |
title_fullStr | Contribution of Immune Cells to Glucocorticoid Receptor Expression in Breast Cancer |
title_full_unstemmed | Contribution of Immune Cells to Glucocorticoid Receptor Expression in Breast Cancer |
title_short | Contribution of Immune Cells to Glucocorticoid Receptor Expression in Breast Cancer |
title_sort | contribution of immune cells to glucocorticoid receptor expression in breast cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370149/ https://www.ncbi.nlm.nih.gov/pubmed/32629782 http://dx.doi.org/10.3390/ijms21134635 |
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