Meta-Analysis of steroid-converting enzymes and related receptors in prostate cancer suggesting novel combined therapies.

Abstract

Androgen receptor (AR) signaling is essential for prostate cancer (PC) progression and treatment. Experiments have demonstrated that the intratumoral androgen levels are not affected by circulating androgen levels, but rather modulated by local steroid-converting enzyme activities. The expression modulation status of human steroid-converting enzymes and nuclear receptors are of great promise to identify novel therapeutic targets. Meta-analysis was performed with 9 cohorts (1093 specimens) from Gene Expression Omnibus, 16 cohorts (933 specimens) from Oncomine and the TCGA cohort (550 specimens). We found significant up regulation of 5α-reductase type 1 and type 3 in both primary and metastatic PC, together with the down regulation of AKR1C2 in primary PC, contributing to the high intratumoral DHT levels. The expression of AR in metastatic PC was up regulated, indicating the importance of AR signaling in the progression of this cancer. The down regulations of HSD11B1 and NR3C1 in primary and metastatic PC may diminish the anti-inflammation and anti-proliferation effects of glucocorticoids signaling. Furthermore, the decrease of progesterone receptor (PGR) expression in primary and metastatic PC was also observed, relieving the suppression effect of PGR on PC proliferation. The clinical evidences of the remarkable expression modulation of steroid-converting enzymes and receptors in PC may indicate novel combined treatment against this highly incident cancer.

• Authors: Wen-Fa Zhang, Tang Li, Sheng-Xiang Lin
• Journal: The Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 198 Pg. 105559 (04 2020) ISSN: 1879-1220 [Electronic] England
• PMID: 31783154 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• NR3C1 protein, human
• Receptors, Androgen
• Receptors, Glucocorticoid
• Receptors, Progesterone
• Hydroxysteroid Dehydrogenases
• 11-beta-Hydroxysteroid Dehydrogenase Type 1
• HSD11B1 protein, human
• AKR1C2 protein, human
• 3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Topics

• 11-beta-Hydroxysteroid Dehydrogenase Type 1 (genetics)
• 3-Oxo-5-alpha-Steroid 4-Dehydrogenase (genetics)
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Humans
• Hydroxysteroid Dehydrogenases (genetics)
• Male
• Prostatic Neoplasms (enzymology, genetics, pathology)
• Receptors, Androgen (genetics)
• Receptors, Glucocorticoid (genetics)
• Receptors, Progesterone (genetics)
• Up-Regulation