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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...

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Autores principales: Wu, Kan, Liu, Zhihong, Liang, Jiayu, Zhang, Fuxun, Zhang, Fan, Wang, Yaohui, Lia, Thongher, Liu, Shenzhuo, Zhu, Yuchun, Li, Xiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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.
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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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