Plasma proteasomal chymotrypsin-like activity correlates with prostate cancer progression

• Published in: Tumor biology Vol. 36; no. 6; pp. 4115 - 4121
• Main Authors: Deng, Xiangrong, Zhou, Ping, Wei, Xinghua, Uhlman, Matthew, Lin, Yurong, Lin, Xuanting, Wu, Sifeng, Diao, Pengfei, Xie, Haiqing, Liu, Jinbao, Xie, Keji, Tang, Ping
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.06.2015; Springer Nature B.V
• Subjects: Aged; Antigens; Apoptosis; bcl-2-Associated X Protein - biosynthesis; Biomarkers; Biomarkers, Tumor - biosynthesis; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Blood Proteins - biosynthesis; Blood Proteins - genetics; Cancer Research; Cell Line, Tumor; Disease Progression; Gene Expression Regulation, Neoplastic; HSP72 Heat-Shock Proteins - biosynthesis; Humans; Male; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Proteases; Proteasome Endopeptidase Complex - genetics; Research Article; Risk Factors; Ubiquitinated Proteins - biosynthesis; Xenograft Model Antitumor Assays; Proteasomal activity; Biomarker; Prostate cancer; Chymotrypsin-like
• ISSN: 1010-4283; 1423-0380; 1423-0380
• DOI: 10.1007/s13277-015-3045-7

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.