European urology oncology · 2025
Prognostic Significance of the Cytoplasmic Expression of UDP-glucuronosyltransferase 2B17 in Localized Prostate Cancer: Insights from the Canadian Prostate Cancer Biomarker Network and PROCURE Multi-institutional Cohorts.
СтатьяМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Uchil Ashwini, Lacombe Louis, Hovington Hélène, Brisson Hervé, Simonyan David, Caron Patrick, Ouellet Véronique, Latour Mathieu, Aprikian Armen, Bergeron Alain, Chevalier Simone, McKercher Ginette, Brimo Fadi, Fazli Ladan, Fleshner Neil, Gleave Martin, Karakiewicz Pierre I, Carmel Michel, Hamilou Zineb, Trudel Dominique, van der Kwast Theodorus, Mes-Masson Anne-Marie, Dong Xuesen, Saad Fred, Guillemette Chantal, Lévesque Eric
Аннотация
BACKGROUND AND OBJECTIVE: Prostate cancer (PCa) is hormone dependent, with UDP-glucuronosyltransferase 2B17 (UGT2B17) playing a central role in androgen inactivation. This study aimed to evaluate whether UGT2B17 expression in prostatectomy specimens can serve as a prognostic marker for lethal PCa.
METHODS: A prespecified hypothesis posited that UGT2B17 expression (>25%) in primary tumors is associated with an aggressive disease phenotype, leading to metastasis, castration resistance (castration-resistant PCa [CRPC]), and mortality in men initially diagnosed with localized disease. Two high-density prostate tumor tissue microarray datasets were analyzed: the first from the Canadian Prostate Cancer Biomarker Network biobank (n = 1454) and the second from the PROCURE cohort (n = 1562). Kaplan-Meier and Cox proportional hazard ratio analyses were used to evaluate metastasis-free survival, CRPC, and PCa-specific mortality. Steroid levels were measured in plasma samples by mass spectrometry, and a linear regression model was used to evaluate variations in hormone levels based on tumoral UGT2B17 expression.
KEY FINDINGS AND LIMITATIONS: UGT2B17 was associated with prognostic factors and linked to elevated levels of androsterone glucuronide (60%), the major circulating androgen-inactive metabolite, which is inactivated by UGT2B17. Kaplan-Meier and multivariable Cox analyses revealed that higher tumoral UGT2B17 is associated with an increased risk of progression to metastatic/CRPC stages and with PCa-specific mortality.
CONCLUSIONS AND CLINICAL IMPLICATIONS: UGT2B17 expression influences hormone levels and identifies a subset of patients at an increased risk of progression to an incurable disease stage. Findings support the notion that enhanced UGT2B17, through increased androgen inactivation, creates a low-androgen tumor environment that drives tumor progression to a more aggressive phenotype.
METHODS: A prespecified hypothesis posited that UGT2B17 expression (>25%) in primary tumors is associated with an aggressive disease phenotype, leading to metastasis, castration resistance (castration-resistant PCa [CRPC]), and mortality in men initially diagnosed with localized disease. Two high-density prostate tumor tissue microarray datasets were analyzed: the first from the Canadian Prostate Cancer Biomarker Network biobank (n = 1454) and the second from the PROCURE cohort (n = 1562). Kaplan-Meier and Cox proportional hazard ratio analyses were used to evaluate metastasis-free survival, CRPC, and PCa-specific mortality. Steroid levels were measured in plasma samples by mass spectrometry, and a linear regression model was used to evaluate variations in hormone levels based on tumoral UGT2B17 expression.
KEY FINDINGS AND LIMITATIONS: UGT2B17 was associated with prognostic factors and linked to elevated levels of androsterone glucuronide (60%), the major circulating androgen-inactive metabolite, which is inactivated by UGT2B17. Kaplan-Meier and multivariable Cox analyses revealed that higher tumoral UGT2B17 is associated with an increased risk of progression to metastatic/CRPC stages and with PCa-specific mortality.
CONCLUSIONS AND CLINICAL IMPLICATIONS: UGT2B17 expression influences hormone levels and identifies a subset of patients at an increased risk of progression to an incurable disease stage. Findings support the notion that enhanced UGT2B17, through increased androgen inactivation, creates a low-androgen tumor environment that drives tumor progression to a more aggressive phenotype.