Introduction/Background JARID1A and JARID1B (jumonji-A/T-rich-interactive-domain) belong to the family of lysine specific demethylases. Both can remove tri- and di-methyl marks from H3K4 (histone-3, lysine-4) and are overexpressed in many tumors. In ovarian cancer (OC) JARID1A leads to proliferation and metastasis. High JARID1B mRNA-expression is associated with poor outcome and chemoresistance in OC. The aim of this study was to explore the role of JARID1A- and JARID1B-mRNA-expression in OC.

Methodology JARID1A and JARID1B mRNA-expression was investigated in 238 epithelial OCs and put in relation to clinicopathological characteristics. Univariate and multivariate survival analyses were used to explore the association of both demethylases with patients’ outcome. Additionally, nineteen non-neoplastic fallopian tubal and sixteen non-neoplastic ovarian samples were used as a control group.

Results High JARID1B mRNA-expression was associated with worse PFS and OS in the whole cohort, which could be confirmed in multivariate Cox-regression analysis (HR=1.638, P=0.011 and HR=1.618, P=0.009). Interestingly, in the subgroup of high-grade OCs high JARID1A mRNA-expression was associated with better PFS and OS (HR=1.538, P=0.004 and HR=1.578, P=0.007).

Conclusion Although, JARDID1A and JARID1B are so far thought to have the same biological functions, we showed for the first time that high JARID1A expression is independently associated with favorable PFS and OS in high-grade OCs, whereas high JARID1B mRNA-expression is associated with worse clinical outcome. These findings suggest that potential targeted therapies on chromatin modulation by histone demethylation should be carefully tailored by considering the opposite prognostic effects of both demethylases.

Disclosures No Disclosures.