Intracellularly, the ubiquitin-proteasome system participates in crucial functions such as cell cycling, differentiation, proliferation, gene transcription, and apoptosis. However, in malignancies including ovarian cancer increased extracellular concentrations of circulating 20S proteasomes (c-proteasomes) have been detected in blood. We tested the hypothesis that the c-proteasome plasma concentration is a biomarker associated with the clinical course of ovarian cancer patients.

20S-proteasome venous plasma concentration was measured by ELISA in patients presenting with ovarian cancer before (n=120) and after (n=68) primary treatment, and in healthy volunteers (n=55). The median follow-up time was 19months. To assess the relation of proteasome expression with c-proteasome concentration, tumor specimens from 27 patients were immunohistochemically stained for 20S proteasome using an antibody directed against the core subunits of the catalytic domain of the 20S proteasome.

Median c-proteasome concentration was higher (p<0.0001) in untreated ovarian cancer patients (457.5ng/ml, range: 200-12540ng/ml) than in healthy controls 290ng/ml, range: 140-425ng/ml). Following completion of primary treatment, the median c-proteasome concentration increased (p=0.003) relative to baseline (595ng/ml, range: 200-20000ng/ml) and concentrations positively correlated (p=0.031) with residual disease left at primary surgery. Patients with post-treatment c-proteasome concentrations exceeding the cohort's median showed a diminished survival (p=0.045). We found no correlation between c-proteasome concentration and strength of proteasomal staining in tumor specimens.

Circulating proteasome concentrations correlate with residual tumor mass and might be a prognostic variable in ovarian cancer following primary therapy.Copyright © 2010 Elsevier Inc. All rights reserved.

PMID: 21075439 [PubMed - as supplied by publisher] Source: National Library of Medicine.