Cancer Res. 2015 Sep 11. pii: canres.3569.2014. [Epub ahead of print]

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

Turcotte M¹, Spring K¹, Pommey S¹, Chouinard G¹, Cousineau I¹, George J², Chen GM³, Gendoo DM³, Haibe-Kains B³, Karn T⁴, Rahimi K¹, Le Page C⁵,Provencher D⁵, Mes-Masson AM⁵, Stagg J⁶.

Abstract

The cell surface nucleotidase CD73 is an immunosuppressive enzyme involved in tumor progression and metastasis. While 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 HGS ovarian cancer patients. 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 (EMT) gene signature. Moreover, in vitro studies revealed that CD73 and extracellular adenosine enhance ovarian tumor cell growth as well as expression of anti-apoptotic BCL-2 family members. Finally, in vivo co-injection 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.