Tumor Biology

, Volume 36, Issue 6, pp 4115–4121 | Cite as

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
Research Article

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.

Keywords

Chymotrypsin-like Proteasomal activity Prostate cancer Biomarker 

Abbreviations

PCa

Prostate cancer

CT-like

Chymotrypsin-like

PSA

Prostate-specific antigen

DRE

Digital rectal examination

TRUS

Transrectal ultrasound

UPS

Ubiquitin proteasome system

PV

Prostate volume

AUA

American Urological Association

Notes

Acknowledgments

This work was supported by a Key Project of Guangzhou Municipal Health Bureau Grant, China (No. 20121A021006) and a National Natural Science Foundation (No.81072091/H1619) to Ping Tang. We thank Dr. Xinlin Chen for his help with statistical analysis.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Xiangrong Deng
    • 1
  • Ping Zhou
    • 2
  • Xinghua Wei
    • 1
  • Matthew Uhlman
    • 3
  • Yurong Lin
    • 4
  • Xuanting Lin
    • 1
  • Sifeng Wu
    • 1
  • Pengfei Diao
    • 1
  • Haiqing Xie
    • 1
  • Jinbao Liu
    • 2
  • Keji Xie
    • 1
  • Ping Tang
    • 1
  1. 1.Department of Urology, Guangzhou First People’s HospitalGuangzhou Medical UniversityGuangzhouChina
  2. 2.Protein Modification and Degradation Lab, Department of PathophysiologyGuangzhou Medical UniversityGuangzhouChina
  3. 3.Department of UrologyUniversity of IowaIowa CityUSA
  4. 4.Department of UrologyJieyang People’s HospitalJieyangChina

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