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

Abstract

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.

Discovery of a glucocorticoid receptor (GR) activity signature correlates with immune cell infiltration in adrenocortical carcinoma

“… 20 Our earlier study provided initial insights into the role of GR in ACC through immunohistochemistry and bioinformatics analysis and discovered that patients with low GR expression often exhibited excess glucocorticoid secretion and a dismally poor prognosis. 21 These data emphasize the vital roles of GR signaling in the immune microenvironment composition.…”

“…Details on cohort construction, patient selection, characteristics, treatment, and follow-up protocol have been described in our previous report. 21 The GR status has been previously reviewed. Briefly, an anti-GR monoclonal antibody (#12041, 1:400, Cell Signaling Technology (CST)) was employed to assess the expression level of GR in primary tumors using immunohistochemistry.…”

Comprehensive analysis of an ATF/CREB family-based signature with regard to prognosis and immune feature in adrenocortical carcinoma

“…Formalin-xed, para n-embedded (FFPE) tissues from our study cohort was used for immunostaining using anti-ATF4 rabbit polyclonal antibody (dilution ratio 1:100; FNab00662; FineTest; Wuhan, CN), following established standard protocols as previously described [21] . A semi-quantitative scoring system was used to quantify the ATF4 staining based on the intensity and extent of staining.…”