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Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma
Adrenocortical carcinoma (ACC) is a rare endocrine tumor, and most cases present with hormone excess with poor prognosis. Our research aims to determine the clinical and biological significance of glucocorticoid receptor (GR) expression using large cohorts of ACC patients. Immunohistochemistry was u...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389328/ https://www.ncbi.nlm.nih.gov/pubmed/35992138 http://dx.doi.org/10.3389/fendo.2022.903824 |
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author | Wu, Kan Liu, Zhihong Liang, Jiayu Zhang, Fuxun Zhang, Fan Wang, Yaohui Lia, Thongher Liu, Shenzhuo Zhu, Yuchun Li, Xiang |
author_facet | Wu, Kan Liu, Zhihong Liang, Jiayu Zhang, Fuxun Zhang, Fan Wang, Yaohui Lia, Thongher Liu, Shenzhuo Zhu, Yuchun Li, Xiang |
author_sort | Wu, Kan |
collection | PubMed |
description | Adrenocortical carcinoma (ACC) is a rare endocrine tumor, and most cases present with hormone excess with poor prognosis. Our research aims to determine the clinical and biological significance of glucocorticoid receptor (GR) expression using large cohorts of ACC patients. Immunohistochemistry was used to assess the expression of GR in 78 ACC cases from the West China Hospital (WCH) cohort. RNA-seq data were retrieved from The Cancer Genome Atlas database (TCGA, n=79). Clinicopathological and follow-up data were obtained from two cohorts. The correlation between the GR gene and tumor immune status was estimated using TIMER and GEPIA2. Kaplan–Meier analysis was performed to identify the prognostic value of GR in ACC. In the WCH cohort, positive nuclear GR staining was identified in 90% of the primary ACC cases. Cortisol-secreting ACCs demonstrated significantly lower GR protein expression than did nonfunctioning tumors (P<0.001). This finding was validated by the mRNA data analysis of the TCGA cohort (P = 0.030). GR expression was found to be positively correlated with the immune cell infiltration level and immune-checkpoint-related gene expression in ACC. Survival comparison and multivariate analysis showed that GR expression is an independent prognostic predictor of disease-free survival and overall survival in ACC patients in both cohorts. Our findings suggest that low GR expression is significantly correlated with excess cortisol, immune signatures and poor survival in ACC patients. We propose that GR signaling may play an important role in ACC behavior and thus may be a therapeutic target, which deserves further research. |
format | Online Article Text |
id | pubmed-9389328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93893282022-08-20 Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma Wu, Kan Liu, Zhihong Liang, Jiayu Zhang, Fuxun Zhang, Fan Wang, Yaohui Lia, Thongher Liu, Shenzhuo Zhu, Yuchun Li, Xiang Front Endocrinol (Lausanne) Endocrinology Adrenocortical carcinoma (ACC) is a rare endocrine tumor, and most cases present with hormone excess with poor prognosis. Our research aims to determine the clinical and biological significance of glucocorticoid receptor (GR) expression using large cohorts of ACC patients. Immunohistochemistry was used to assess the expression of GR in 78 ACC cases from the West China Hospital (WCH) cohort. RNA-seq data were retrieved from The Cancer Genome Atlas database (TCGA, n=79). Clinicopathological and follow-up data were obtained from two cohorts. The correlation between the GR gene and tumor immune status was estimated using TIMER and GEPIA2. Kaplan–Meier analysis was performed to identify the prognostic value of GR in ACC. In the WCH cohort, positive nuclear GR staining was identified in 90% of the primary ACC cases. Cortisol-secreting ACCs demonstrated significantly lower GR protein expression than did nonfunctioning tumors (P<0.001). This finding was validated by the mRNA data analysis of the TCGA cohort (P = 0.030). GR expression was found to be positively correlated with the immune cell infiltration level and immune-checkpoint-related gene expression in ACC. Survival comparison and multivariate analysis showed that GR expression is an independent prognostic predictor of disease-free survival and overall survival in ACC patients in both cohorts. Our findings suggest that low GR expression is significantly correlated with excess cortisol, immune signatures and poor survival in ACC patients. We propose that GR signaling may play an important role in ACC behavior and thus may be a therapeutic target, which deserves further research. Frontiers Media S.A. 2022-08-05 /pmc/articles/PMC9389328/ /pubmed/35992138 http://dx.doi.org/10.3389/fendo.2022.903824 Text en Copyright © 2022 Wu, Liu, Liang, Zhang, Zhang, Wang, Lia, Liu, Zhu and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Wu, Kan Liu, Zhihong Liang, Jiayu Zhang, Fuxun Zhang, Fan Wang, Yaohui Lia, Thongher Liu, Shenzhuo Zhu, Yuchun Li, Xiang Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma |
title | Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma |
title_full | Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma |
title_fullStr | Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma |
title_full_unstemmed | Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma |
title_short | Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma |
title_sort | expression of glucocorticoid receptor (gr) and clinical significance in adrenocortical carcinoma |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9389328/ https://www.ncbi.nlm.nih.gov/pubmed/35992138 http://dx.doi.org/10.3389/fendo.2022.903824 |
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