UDP-glucuronosyltransferases and biochemical recurrence in prostate cancer progression

BMC Cancer

Research Article

Stephen J. Freedland¹  Adriana C. Vidal¹  Delores J. Grant²  Skyla T. Carney²  Lauren E. Howard³  Zinan Chen³  Clara E. Magyar⁴  Jill Squires⁴  Jiaoti Huang⁴  Amanda De Hoedt⁵  Emily Wiggins⁵ 

[1] Cedars-Sinai Health System, Center for Integrated Research on Cancer and Lifestyle, Cancer Genetics and Prevention Program, Surgery, 8700 Beverly Blvd, 90048, Los Angeles, CA, USA;Department of Biological and Biomedical Science, Cancer Research Program, North Carolina Central University, Julius L. Chambers Biomedical/Biotechnology Research Institute, 1801 Fayetteville Street, 27707, Durham, NC, USA;Department of Biostatistics and Bioinformatics, Duke University Medical Center, Box 2721, 2424 Erwin Road, Suite 1102 Hock Plaza, 27710, Durham, NC, USA;Department of Pathology and Laboratory Medicine, University of California at Los Angeles, The David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, CHS 14-112, 90095, Los Angeles, CA, USA;Durham Veterans Administration Medical Center, 508 Fulton St, 27705, Durham, NC, USA;

关键词: Prostate cancer;    Biochemical recurrence;    UDP-glucuronosyltransferases;    UGT2B17;   

DOI  :  10.1186/s12885-017-3463-6

 received in 2016-05-19, accepted in 2017-06-28,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundUridine 5′-diphosphate-glucuronosyltransferase 2B (UGT2B) genes code for enzymes that catalyze the clearance of testosterone, dihydrotestosterone (DHT), and DHT metabolites in the prostate basal and luminal tissue. The expression of the UGT2B15, UGT2B17, and UGT2B28 enzymes has not been evaluated in prostate tissue samples from hormone therapy-naïve patients.MethodsWe determined the expression of UGT2B15, UGT2B17, and UGT2B28 enzymes in 190 prostate tissue samples from surgical specimens of a multiethnic cohort of patients undergoing radical prostatectomy at the Durham Veterans Affairs Medical Center. The association between each protein’s percent positive and H-score, a weighted score of staining intensity, and the risk of biochemical recurrence (BCR) was tested using separate Cox proportional hazards models. In an exploratory analysis, UGT2B17 total positive and H-score were divided at the median and we tested the association between UGT2B17 group and risk of BCR.ResultsThe median follow-up for all patients was 118 months (IQR: 85-144). Of 190, 83 (44%) patients developed BCR. We found no association between UGT2B15 or UGT2B28 and risk of BCR. However, there was a trend for an association between UGT2B17 and BCR (HR = 1.01, 95% CI 1.00-1.02, p = 0.11), though not statistically significant. Upon further investigation, we found that patients with UGT2B17 higher levels of expression had a significant increased risk of BCR on univariable analysis (HR = 1.57, 95% CI 1.02-2.43, p = 0.041), although this association was attenuated in the multivariable model (HR = 1.50, 95% CI 0.94-2.40, p = 0.088).ConclusionsOur findings suggest that UGT2B17 overexpression may be associated with a significant increased risk of BCR. These results are consistent with previous reports which showed UGT2B17 significantly expressed in advanced prostate cancer including prostate tumor metastases.

【 授权许可】

CC BY   
© The Author(s). 2017