Plasma proteasomal chymotrypsin-like activity correlates with prostate cancer progression.

Xiangrong Deng, Ping Zhou, Xinghua Wei, Matthew Uhlman, Yurong Lin, Xuanting Lin, Sifeng Wu, Pengfei Diao, Haiqing Xie, Jinbao Liu, Keji Xie, Ping Tang

Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 2015 Jun

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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.

Citation

Xiangrong Deng, Ping Zhou, Xinghua Wei, Matthew Uhlman, Yurong Lin, Xuanting Lin, Sifeng Wu, Pengfei Diao, Haiqing Xie, Jinbao Liu, Keji Xie, Ping Tang. Plasma proteasomal chymotrypsin-like activity correlates with prostate cancer progression. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2015 Jun;36(6):4115-21