The prognostic impact of circulating proteasome concentrations in patients with epithelial ovarian cancer

Gynecol Oncol. 2011 Feb;120(2):233-8. doi: 10.1016/j.ygyno.2010.10.014. Epub 2010 Nov 13.


Background: 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.

Methods: 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 19 months. 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.

Results: Median c-proteasome concentration was higher (p<0.0001) in untreated ovarian cancer patients (457.5 ng/ml, range: 200-12540 ng/ml) than in healthy controls 290 ng/ml, range: 140-425 ng/ml). Following completion of primary treatment, the median c-proteasome concentration increased (p=0.003) relative to baseline (595 ng/ml, range: 200-20000 ng/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.

Conclusions: Circulating proteasome concentrations correlate with residual tumor mass and might be a prognostic variable in ovarian cancer following primary therapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Ovarian Epithelial
  • Case-Control Studies
  • Female
  • Humans
  • Middle Aged
  • Neoplasm, Residual / blood
  • Neoplasm, Residual / pathology
  • Neoplasms, Glandular and Epithelial / blood
  • Neoplasms, Glandular and Epithelial / enzymology
  • Neoplasms, Glandular and Epithelial / surgery
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / surgery
  • Prognosis
  • Proteasome Endopeptidase Complex / blood*
  • Ubiquitin / blood
  • Young Adult


  • Ubiquitin
  • Proteasome Endopeptidase Complex