783P - The role of JARID1B in ovarian cancer

Background

JARID1B (jumonji A/T rich interactive domain) is a lysine specific demethylase which is able to remove tri- and di-methyl marks from H3K4 (histone 3 – H3, lysine 4 – K4). It is overexpressed in many tumors. In ovarian cancer (OC) high JARID1B mRNA-expression is associated with poor outcome and chemoresistance. The aim of this study was to explore the role of JARID1B mRNA-expression in OC.

Methods

JARID1B mRNA-expression was investigated in 238 epithelial OCs and put in relation to clinicopathological characteristics, BRCA1/2-mutational status, homologous recombination deficiency (HRD) status and BRCA1/2 mRNA-expression levels. Additionally, nineteen non-neoplastic fallopian tubal and sixteen non-neoplastic ovarian samples were used as a control group.

Results

JARID1B mRNA-expression in OCs was significantly higher compared to non-neoplastic tubal and ovarian tissue (P<0.001 and P=0.003, respectively). High JARID1B mRNA-expression was associated with worse PFS and OS in univariate analysis, which could be confirmed in multivariate Cox-regression analysis (PFS: HR=1.577, P=0.035 and OS: HR=1.710, P=0.009). A strong correlation between JARID1B and BRCA1/2 mRNA-expression was found (r²=0.233, P=0.001 and r²0.196, P=0.011; respectively). JARID1B expression was significantly lower in BRCA1-mutated OCs compared to BRCA1 wild-type cancers (P=0.021). Regarding BRCA2 mutational status, no significant differences in JARID1B expression between wildtype and mutated cancers were revealed. In tumors with HRD levels of JARID1B were significantly lower compared to HR proficient tumors (P=0.006).

Conclusions

High JARID1B mRNA-expression is associated with worse PFS and OS. As JARID1B is known to inhibit the expression of the anti-angiogenic and anti-metastatic epithelial chemokine CCL14 it is conceivable that the low JARID1B expression observed in BRCA1-mutated cancers may contribute to the better prognosis generally seen in these cancers. This could also be underlined by the significant lower levels of JARID1B expression in cancers with high HRD scores. In order to further investigate the role of JARID1B in OC analyses on its interplay with CCL14 are ongoing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.