Isabelle Bairati

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

Publisher: Elsevier BV

Date: 06-2019

DOI: 10.1016/J.PRP.2019.02.019

Abstract: 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.

Université Laval

Location: Canada

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Université De Franche-Comté Sciences Séparatives Biologiques Et Pharmaceutiques

Location: France

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Fred Hutchinson Cancer Research Center

Location: United States of America

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Universite Laval

Location: Canada

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Centre De Recherche Sur Le Cancer De L'université Laval

Location: Canada

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Centre Intégré Universitaire De Santé Et De Services Sociaux De La Capitale-Nationale

Location: Canada

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Centre De Recherche Du CHUQ

Location: Canada

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Université Laval

Location: No location found

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