AUTHOR=Wu Kan , Liu Zhihong , Liang Jiayu , Zhang Fuxun , Zhang Fan , Wang Yaohui , Lia Thongher , Liu Shenzhuo , Zhu Yuchun , Li Xiang 

TITLE=Expression of glucocorticoid receptor (GR) and clinical significance in adrenocortical carcinoma

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.903824

DOI=10.3389/fendo.2022.903824

ISSN=1664-2392

ABSTRACT=Adrenocortical carcinoma (ACC) is a rare endocrine tumor and most cases present with hormone excess with poor prognosis. Recently, we discovered that the glucocorticoid receptor (GR) is significantly down-regulated in cortisol-secreting ACCs compared with nonfunctioning tumors. Our research aims to determine the clinical and biological significance of GR expression using large cohorts of ACC patients. Immunohistochemistry was used to assess the expression of GR in 78 ACC cases from 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 the TIMER and GEPIA2. Kaplan-Meier analysis were performed to identify the prognostic value of GR in ACC. In the WCH cohort, positive nuclear staining of GR was identified in 90% of the primary ACC. 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 TCGA cohort (P = 0.030). GR expression was found to be positively correlated the immune cell infiltration level 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 cortisol excess, immune signatures and poor survival in ACC patients. We propose that GR signaling may play an important role in ACC behaviour, and thus may be a therapeutic target, deserves further research.