JARID1A is associated with improved prognosis in epithelial high-grade ovarian cancer

JARID1A is a histone demethylase involved in cell cycle regulation, epigenetic remodeling, and cancer progression. While it has been associated with tumor-promoting processes such as epithelial-to-mesenchymal transition and chemoresistance in several cancer types, its exact role in ovarian cancer remains poorly defined. In this study, we analyzed JARID1A mRNA-expression in a well-characterized cohort of 179 epithelial ovarian cancers (OC), with a focus on advanced high-grade serous and endometrioid subtypes (HGOC). High JARID1A expression was significantly associated with unfavorable tumor features, including advanced FIGO stage (P=0.016), high tumor grade (P<0.001) and adverse molecular markers. However, prognostically it was linked to improved progression-free and overall survival (P=0.001 and P=0.001, respectively) and remained an independent predictor of favorable prognosis in multivariate analysis (HR=0.44 for PFS (P=0.001), HR=0.49 for OS (P=0.006). This was also corroborated by validation with external data sets. It is tempting to speculate that in advanced HGOC high JARID1A expression may contribute to growth-inhibitory mechanisms or less proliferative tumor states, despite its association with established markers of aggressiveness. Taken together, our findings identify JARID1A mRNA-expression as a favorable prognostic marker, whose therapeutic inhibition should, at present, be approached with caution in high-grade ovarian cancer.