title: Plasma proteasomal chymotrypsin-like activity correlates with prostate cancer progression.
abstract: Previously, we demonstrated that inhibition of proteasomal chymotrypsin-like (CT-like) activity in human prostate cancer (PCa) PC-3 cultures and PC-3 xenografts results in accumulation of ubiquitinated proteins, followed by induction of cell death. Studies have shown that plasma CT-like proteasomal activity may be a powerful biomarker for risk stratification in hematologic malignancies. We hypothesized that circulating proteasomes could also be used to stratify risk for patients with PCa. A total of 109 patients with suspected PCa underwent prostatic biopsies were enrolled. Subjects were divided into non-cancer, low-risk PCa, and high-risk PCa groups. Three different proteasomal activity markers (CT-like, caspase-like, and trypsin-like) were measured and compared among the three groups. The proteasomal target proteins, Ub-prs, Hsp70, Bax, and P27 in plasma and prostate tissues were also evaluated. Multivariate analysis was used to assess whether CT-like activity was a predictor of PCa progression. Only proteasomal CT-like activity in the high-risk group was statistically higher than in the non-cancer group (P < 0.05). The expression of Ub-prs, Hsp70, Bax, and P27 protein was decreased in both plasma and PCa tissue of high-risk patients. CT-like activity was found to be an independent predictor of high-risk PCa. Subjects with CT-like activity ≥55 had a 2.15-fold higher risk of having high-risk PCa as compared to those with a CT-like activity of <55 (P = 0.021). We found CT-like activity to be an independent predictor of high-risk PCa, and as such, it may be a good candidate as a biomarker for high-risk PCa detection and stratification.
authors.affiliation: Department of Urology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, 510180, Guangdong, China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Deng
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Xinghua
authors.initials: X
authors.lastname: Wei
authors.forename: Matthew
authors.initials: M
authors.lastname: Uhlman
authors.forename: Yurong
authors.initials: Y
authors.lastname: Lin
authors.forename: Xuanting
authors.initials: X
authors.lastname: Lin
authors.forename: Sifeng
authors.initials: S
authors.lastname: Wu
authors.forename: Pengfei
authors.initials: P
authors.lastname: Diao
authors.forename: Haiqing
authors.initials: H
authors.lastname: Xie
authors.forename: Jinbao
authors.initials: J
authors.lastname: Liu
authors.forename: Keji
authors.initials: K
authors.lastname: Xie
authors.forename: Ping
authors.initials: P
authors.lastname: Tang
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001798:Blood Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D050884:HSP72 Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D012307:Risk Factors; D057149:Ubiquitinated Proteins / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: C494826:BAX protein, human; D014408:Biomarkers, Tumor; D001798:Blood Proteins; D050884:HSP72 Heat-Shock Proteins; D057149:Ubiquitinated Proteins; D051028:bcl-2-Associated X Protein; C015078:chymotrypsin-like cationic protein, human; D046988:Proteasome Endopeptidase Complex