Clinical validation of a DNA methylation biomarker associated with overall survival of relapsed ovarian cancer patients.
- Abstract:
- Approximately 70% of ovarian cancer (OC) patients relapse after chemotherapy, underscoring the need to assess survival before second-line treatment. We previously identified PLAT-M8, an 8-CpG blood-based methylation signature linked to chemoresistance. This study validates its correlation with clinicopathological features and treatment profiles in additional cohorts. Extracted DNA from whole blood was provided from the BriTROC-1 (n = 47) and OV04 cohorts (n = 57) upon the first relapse. Additional samples from Hammersmith Hospital (n = 100) were collected during first-line chemotherapy (Cycles 3-4 and 6). Bisulphite pyrosequencing was used to quantify DNA methylation at the previously identified 8 CpG sites. The methylation data obtained were combined with previous data from ScoTROC-1D and 1V (n = 141) and OCTIPS (n = 46). Cox regression was used to assess OS after relapse concerning clinicopathological characteristics. The DNA methylation Class (Class 1 vs. 2) was determined by consensus clustering. As for results, blood DNA methylation at relapse correlates with clinical outcomes, but it has no impact during first-line treatment. Class 1 is linked to shorter survival (summary OS: HR 2.50, 1.64-3.79) and poorer prognosis on carboplatin monotherapy (OS: aHR 9.69, 95% CI: 2.38-39.47). It is associated with older (>75 years), advanced-stage, platinum-resistant patients, residual disease, and shorter PFS. In contrast, Class 2 is linked to platinum sensitivity, higher complete response rates (RECIST), and better prognosis but shows no correlation with CA-125. These findings highlight PLAT-M8's potential in guiding second-line chemotherapy decisions. The PLAT-M8 methylation biomarker is associated with survival in relapsed OC patients and may potentially predict their response to second-line platinum treatment.
- Authors:
- M Habiburrahman, N Masrour, N Patel, AM Piskorz, R Brown, JD Brenton, IA McNeish, JM Flanagan
- Journal:
- Int J Cancer
- Publication date:
- 1st Nov 2025
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- DOI