Expression and clinical significance of androgen receptor in bladder cancer: A meta-analysis

Abstract

Abstract. Emerging evidence has demonstrated that androgen receptor (AR) is a promising therapeutic target for bladder cancer. However, the relationship between AR expression and its clinical significance remains controversial. The present in-depth meta-analysis aimed to investigate the correlation between AR expression and clinicopathological features, as well as prognostic value in bladder cancer. A systematic search was performed from PubMed, Web of Knowledge, Embase and the Cochrane Central Search Library by January 2017. The correlation between AR expression and tumor stage, tumor grade, recurrence free survival and progression free survival for patients with bladder cancer was evaluated. A total of 12 relevant studies with 1,652 patient samples were included. AR expression positively correlated with low tumor grade [odds ratio (OR), 1.95; 95% confidence interval (CI), 1.36-2.81], low tumor stage (OR, 2.06; 95% CI, 1.02-4.16) and low recurrence rate [hazard ratio (HR), 0.48; 95% CI, 0.31-0.75] in Caucasian patients. While, its expression had no significant impact on cancer susceptibility (OR, 1.62; 95% CI, P= 0.44) and progression-free survival (HR, 1.20; 95% CI, P=0.77). The present meta-analysis indicated that AR expression correlates with tumor grade, clinical stage and recurrence rates in the specified population and classification system.Further studies are required to determine the precise role of AR in bladder cancer.

Inhibition of Androgen Signalling Improves the Outcomes of Therapies for Bladder Cancer: Results from a Systematic Review of Preclinical and Clinical Evidence and Meta-Analysis of Clinical Studies

“…However, based on the available evidence, these advantages seem to be related to the aggressiveness of the disease. These findings should be interpreted in light of previous evidence demonstrating that, in BCa patients, androgen receptor expression inversely correlates with tumour grade and stage [ 28 ]. Therefore, it can be hypothesized that the lower expression of androgen receptors in patients with high-stage and high-grade tumours may represent the substrate for the lower efficacy of androgen suppression strategies in terms of both recurrence and progression.…”

The Role of Androgens and Androgen Receptor in Human Bladder Cancer

“…Lifestyle, environmental, or occupational factors, such as smoking and industrial chemicals, are believed to contribute to this sex disparity [ 46 ]. Nevertheless, the expression and androgen receptor activity are correlated with bladder cancer [ 47 , 48 , 49 , 50 ]. This correlation could be explained due to the fact that AR signaling negatively regulates the activity of the uridine 5-diphodphoglucoronosyltransferase (UGT) enzymes.…”

“…Male internal genitalia, including urothelium, as well as prostate, are derived from the urothelial sinus endoderm and these tissues require the AR signaling pathway for its differentiation and development. Based on the common origin, a hypothesis has been proposed that AR signaling is involved in the carcinogenesis of bladder cancer [ 48 , 49 , 50 ]. The presence of ARs is associated with the development of bladder cancer.…”

Current Systemic Treatment Options in Metastatic Urothelial Carcinoma after Progression on Checkpoint Inhibition Therapy—A Systemic Review Combined with Single-Group Meta-Analysis of Three Studies Testing Enfortumab Vedotin

“…Thirteen to fifty-three percent of bladder cancer specimens express the androgen receptor (AR), regardless of the patient's sex [90,91]. The density of the AR correlates negatively with staging and grading of the tumor [92,93], indicating that loss of androgen sensitivity is associated with tumor progression [94]. Enzalutamid as a next-generation AR inhibitor is currently being investigated in combination with platinum-based CT in mUC in a phase I/Ib study [95].…”