Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer.


Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM)/ Institut du cancer de Montréal, Montréal, QC, H2X 0A9, Canada; Department of Pathology, Centre Hospitalier de l'Université de Montréal, Montréal, QC, H2X 3O4, Canada; Department of Pathology and Cellular Biology, Faculty of Medicine, Université de Montréal, Montréal, QC, H3T 1J4, Canada; Laval University Cancer Research Center and Research Center of the Centre Hospitalier Universitaire (CHU) de Québec, Ville de Québec, QC, G1R 3S3, Canada. Electronic address: [Email]


Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI - encoding Complement Factor I - and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2-3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2-3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17-4.53) and death (adjusted HR: 3.42; 95% CI: 1.72-6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.


Degradome,High grade serous ovarian carcinoma,Immunohistochemistry,Ovarian carcinoma,Progression-free survival,Proteases,