CD73 is associated with poor prognosis in high-grade serous ovarian cancer.

Autor:	Turcotte M; Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada. Institut du Cancer de Montréal, Montréal, Québec, Canada. Faculté de Pharmacie, Université de Montréal, Québec, Canada., Spring K; Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada. Institut du Cancer de Montréal, Montréal, Québec, Canada., Pommey S; Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada. Institut du Cancer de Montréal, Montréal, Québec, Canada., Chouinard G; Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada. Institut du Cancer de Montréal, Montréal, Québec, Canada., Cousineau I; Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada. Institut du Cancer de Montréal, Montréal, Québec, Canada., George J; Computational Sciences and Statistical Analysis, Jackson Laboratory for Genomic Medicine, Farmington, Connecticut., Chen GM; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Gendoo DM; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Haibe-Kains B; Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada., Karn T; Department of Obstetrics and Gynecology, University Hospital Frankfurt, Germany., Rahimi K; Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada. Department of Medicine, Université de Montréal, Quebec, Canada. Department of Pathology, Centre hospitalier de l'Université de Montréal (CHUM), Quebec, Canada., Le Page C; Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada. Institut du Cancer de Montréal, Montréal, Québec, Canada., Provencher D; Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada. Institut du Cancer de Montréal, Montréal, Québec, Canada. Department of Pathology, Centre hospitalier de l'Université de Montréal (CHUM), Quebec, Canada. Division of Gynecologic-Oncology, Department of Obstectrics and Gynecology, Université de Montréal, Montreal, Canada., Mes-Masson AM; Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada. Institut du Cancer de Montréal, Montréal, Québec, Canada. Department of Pathology, Centre hospitalier de l'Université de Montréal (CHUM), Quebec, Canada. Division of Gynecologic-Oncology, Department of Obstectrics and Gynecology, Université de Montréal, Montreal, Canada., Stagg J; Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Québec, Canada. Institut du Cancer de Montréal, Montréal, Québec, Canada. Faculté de Pharmacie, Université de Montréal, Québec, Canada. john.stagg@umontreal.ca.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2015 Nov 01; Vol. 75 (21), pp. 4494-503. Date of Electronic Publication: 2015 Sep 11.
DOI:	10.1158/0008-5472.CAN-14-3569
Abstrakt:	The cell surface nucleotidase CD73 is an immunosuppressive enzyme involved in tumor progression and metastasis. Although preclinical studies suggest that CD73 can be targeted for cancer treatment, the clinical impact of CD73 in ovarian cancer remains unclear. In this study, we investigated the prognostic value of CD73 in high-grade serous (HGS) ovarian cancer using gene and protein expression analyses. Our results demonstrate that high levels of CD73 are significantly associated with shorter disease-free survival and overall survival in patients with HGS ovarian cancer. Furthermore, high levels of CD73 expression in ovarian tumor cells abolished the good prognosis associated with intraepithelial CD8(+) cells. Notably, CD73 gene expression was highest in the C1/stromal molecular subtype of HGS ovarian cancer and positively correlated with an epithelial-to-mesenchymal transition gene signature. Moreover, in vitro studies revealed that CD73 and extracellular adenosine enhance ovarian tumor cell growth as well as expression of antiapoptotic BCL-2 family members. Finally, in vivo coinjection of ID8 mouse ovarian tumor cells with mouse embryonic fibroblasts showed that CD73 expression in fibroblasts promotes tumor immune escape and thereby tumor growth. In conclusion, our study highlights a role for CD73 as a prognostic marker of patient survival and also as a candidate therapeutic target in HGS ovarian cancers. (©2015 American Association for Cancer Research.)
Databáze:	MEDLINE
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