Abstract
BackgroundTo 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.ResultsThe 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.).ConclusionThe 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.
Highlights
To date, no predictive or prognostic molecular biomarkers except BRCAmutations are clinically estab‐ lished for epithelial ovarian cancer (EOC) despite being the deadliest gynecological malignancy
Germline mutations account for 15–25% of all ovarian carcinoma [5, 6] while somatic mutations of the BRCAgenes are detected in 5–6% of EOC [7, 8]
Samples from patients with known or identified BRCA1/2 mutations (7.5%; n = 15) were evaluated in a separate analysis to exclude any bias caused by the known prognostic value of BRCAmutations [16]
Summary
No predictive or prognostic molecular biomarkers except BRCAmutations are clinically estab‐ lished 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. In the absence of predictive biomarker for any adjuvant treatment, prognostic biomarker may help to identify patients with worse outcome benefitting from maintenance treatment with these new treatment options Both clinical parameters and different molecules or cell populations are targets of intense research to identify and validate prognostic marker. One DNA aberration which can be used as molecular biomarker is CpG hypermethylation belonging to the field of epigenetics
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
