Relationship of tumor glucocorticoid receptor expression with overall survival in ovarian cancer TCGA data

2017 ◽  
Vol 145 ◽  
pp. 33
Author(s):  
J.L.T. Veneris ◽  
L. Huang ◽  
J. Churpek ◽  
S.D. Conzen ◽  
G.F. Fleming
2019 ◽  
Vol 29 (2) ◽  
pp. 357-364 ◽  
Author(s):  
Jennifer Taylor Veneris ◽  
Lei Huang ◽  
Jane E Churpek ◽  
Suzanne D Conzen ◽  
Gini F Fleming

ObjectiveHigh glucocorticoid receptor (GR) protein expression is associated with decreased progression-free survival in ovarian cancer patients and decreased sensitivity to chemotherapy in preclinical models. Prior studies suggest wild type BRCA1 promotes GR activation. The objective of this study was to characterize the relationship of tumor GR gene expression to outcome in ovarian cancer, and to evaluate the relationship of GR expression with BRCA status.MethodsWhole exome and whole genome sequencing, gene expression, and clinical data were obtained for high-grade serous ovarian cancers in The Cancer Genome Atlas. Cases with pathogenic somatic or germline BRCA1 or BRCA2 mutations were identified and classified as BRCA mutated. High or low glucocorticoid receptor expression was defined as expression above or below median of the GR/nuclear receptor subfamily 3 C1 (NR3C1) gene level. Overall survival was estimated by the Kaplan-Meier method and compared by Cox regression analysis.ResultsCombined germline DNA sequencing and tumor microarray expression data were available for 222 high-grade serous ovarian cancer cases. Among these, 47 had a deleterious germline and/or somatic mutation in BRCA1 or BRCA2. In multivariate analysis, high glucocorticoid receptor gene expression was associated with decreased overall survival among ovarian cancer patients, independently of BRCA mutation status. No correlation of GR/NR3C1 gene expression with BRCA mutation status or BRCA1 or BRCA2 mRNA level was observed.ConclusionsIncreased GR gene expression is associated with decreased overall survival in ovarian cancer patients, independently of BRCA mutation status. High-grade serous ovarian cancers with high GR expression and wild type BRCA have a particularly poor outcome.


2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 5545-5545
Author(s):  
Jennifer Taylor Veneris ◽  
Kathleen M. Darcy ◽  
Paulette Mhawech-Fauceglia ◽  
Suzanne D. Conzen ◽  
Gini F. Fleming

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1649
Author(s):  
Noor Bakour ◽  
Frank Moriarty ◽  
Gillian Moore ◽  
Tracy Robson ◽  
Stephanie L. Annett

In solid malignancies, the glucocorticoid receptor (GR) signalling axis is associated with tumour progression and GR antagonists are in clinical development. Therefore, GR expression may be a useful potential prognostic or predictive biomarker for GR antagonist therapy in cancer. The aim of this review is to investigate if GR expression in tumours is predictive of overall survival or progression free survival. Twenty-five studies were identified through systematic searches of three databases and a meta-analysis conducted using a random effects model, quantifying statistical heterogeneity. Subgroup analysis was conducted for cancer types and publication bias was assessed via funnel plots. There was high heterogeneity in meta-analysis of the studies in all cancer types, which found no association between high GR expression with overall survival (pooled unadjusted HR 1.16, 95% CI (0.89–1.50), n = 2814; pooled adjusted HR 1.02, 95% CI (0.77–1.37), n = 2355) or progression-free survival (pooled unadjusted HR 1.12, 95% CI (0.88–1.42), n = 3365; pooled adjusted HR 1.04, 95% CI (0.6–1.81), n = 582) across all cancer types. However, subgroup meta-analyses showed that high GR expression in gynaecological cancers (endometrial and ovarian) (unadjusted HR 1.83, 95% CI (1.31–2.56), n = 664) and early stage, untreated triple negative breast cancers (TNBCs) (unadjusted HR 1.73, 95% CI (1.35–2.23), n = 687) is associated with disease progression. GR expression in late stage, chemotherapy treated TNBC was not prognostic (unadjusted HR 0.76, 95% CI (0.44, 1.32), n = 287). In conclusion, high GR expression is associated with an increased risk of disease progression in gynaecological and early stage, untreated TNBC. Additional studies are required to elucidate the tumour specific function of the GR receptor in order to ensure GR antagonists target the correct patient groups.


2017 ◽  
Vol 146 (1) ◽  
pp. 153-160 ◽  
Author(s):  
Jennifer Taylor Veneris ◽  
Kathleen M. Darcy ◽  
Paulette Mhawech-Fauceglia ◽  
Chunqiao Tian ◽  
Ernst Lengyel ◽  
...  

2015 ◽  
Author(s):  
Narjes Nasiri Ansari ◽  
Eliana Spilioti ◽  
Vasiliki Kalotychou ◽  
Geena Dalagiorgou ◽  
Paraskevi Moutsatsou ◽  
...  

2019 ◽  
Vol 49 (4) ◽  
pp. e13073 ◽  
Author(s):  
Alice G. Vassiliou ◽  
Georgios Floros ◽  
Edison Jahaj ◽  
Georgios Stamogiannos ◽  
Sofianna Gennimata ◽  
...  

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