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Background  To date, no predictive or prognostic molecular biomarkers except  BRCA  mutations are clinically established for epithelial ovarian cancer (EOC) despite being the deadliest gynecological malignancy. Aim of this biomarker study was the analysis of DNA methylation biomarkers for their prognostic value independent from clinical variables in a heterogeneous cohort of 203 EOC patients from two university medical centers.    Results  The marker combination  CAMK2N1/RUNX3  exhibited a significant prognostic value for progression-free (PFS) and overall survival (OS) of sporadic platinum-sensitive EOC ( n  = 188) both in univariate Kaplan–Meier (LogRank  p  < 0.05) and multivariate Cox regression analysis ( p  < 0.05; hazard ratio HR = 1.587).  KRT86  methylation showed a prognostic value only in univariate analysis because of an association with FIGO staging (Fisher’s exact test  p  < 0.01). Thus, it may represent a marker for EOC staging. Dichotomous prognostic values were observed for  KATNAL2  methylation depending on  BRCA  aberrations.  KATNAL2  methylation exhibited a negative prognostic value for PFS in sporadic EOC patients without  BRCA1  methylation (HR 1.591,  p  = 0.012) but positive prognostic value in sporadic EOC with  BRCA1  methylation (HR 0.332,  p  = 0.04) or  BRCA -mutated EOC (HR 0.620, n.s.).    Conclusion  The retrospective analysis of 188 sporadic platinum-sensitive EOC proved an independent prognostic value of the methylation marker combination CAMK2N1/RUNX3 for PFS and OS. If validated prospectively this combination may identify EOC patients with worse prognosis after standard therapy potentially benefiting from intensive follow-up, maintenance therapies or inclusion in therapeutic studies. The dichotomous prognostic value of  KATNAL2  should be validated in larger sample sets of EOC.

clinical epigenetics

CAMK2N1/RUNX3 methylation is an independent prognostic biomarker for progression-free and overall survival of platinum-sensitive epithelial ovarian cancer patients