Abstract
Aldo-keto reductase family 1 member C3 (AKR1C3) is an enzyme in the steroidogenesis pathway, especially in formation of testosterone and dihydrotestosterone, and is believed to have a key role in promoting prostate cancer (PCa) progression, particularly in castration-resistant prostate cancer (CRPC). This study aims to compare the expression level of AKR1C3 between benign prostatic epithelium and cancer cells, and among hormone-naïve prostate cancer (HNPC) and CRPC from the same patients, to understand the role of AKR1C3 in PCa progression. Correlation of AKR1C3 immunohistochemical expression between benign and cancerous epithelia in 134 patient specimens was analyzed. Additionally, correlation between AKR1C3 expression and prostate-specific antigen (PSA) progression-free survival (PFS) after radical prostatectomy was analyzed. Furthermore, we evaluated the consecutive prostate samples derived from 11 patients both in the hormone-naïve and castration-resistant states. AKR1C3 immunostaining of cancer epithelium was significantly stronger than that of the benign epithelia in patients with localized HNPC (p < 0.0001). High AKR1C3 expression was an independent factor of poor PSA PFS (p = 0.032). Moreover, AKR1C3 immunostaining was significantly stronger in CRPC tissues than in HNPC tissues in the same patients (p = 0.0234). Our findings demonstrate that AKR1C3 is crucial in PCa progression.
Highlights
Prostate cancer (PCa) is one of the most commonly diagnosed malignancies and the second leading cause of cancer deaths in the United States [1]
prostate-specific antigen (PSA) progression-free survival (PFS) was estimated by Kaplan–Meier analysis and groups compared with the log-rank test
This is the first study to report that aldo-keto reductase family 1 member C3 (AKR1C3) immunostaining increases along the treatment course, that is, AKR1C3 expression elevates from the hormone-naïve status to the castration-resistant prostate cancer (CRPC) stage in the same patient
Summary
Prostate cancer (PCa) is one of the most commonly diagnosed malignancies and the second leading cause of cancer deaths in the United States [1]. AKR1C3 is known as prostaglandin (PG) F synthase that catalyzes the conversion of PGD2 to 11-βPGF2α and PGF2α prostanoids, contributing to proliferation and radio-resistance in PCa cells [14,15]. All these issues imply that AKR1C3 could have a potential role in PCa biology. We investigated the expression level in hormone-naïve cancer and advanced CRPC in the same patients, to better understand the role of AKR1C3 in PCa progression
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