ArticleJournal of ovarian research2026
Plasma cell-free DNA 5-hydroxymethylcytosine signatures as predictive biomarkers for platinum resistance and prognosis in epithelial ovarian cancer.
Article in Journal of ovarian research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundPlatinum resistance is a major determinant of poor prognosis in epithelial ovarian cancer (EOC); however, no reliable pretreatment biomarkers are currently available to guide first-line therapy. This study aimed to develop a plasma cell-free DNA (cfDNA) 5-hydroxymethylcytosine (5hmC) signature for predicting platinum response and overall survival (OS).
methodsIn this prospective pilot study, pretreatment plasma samples were collected from 63 patients with EOC scheduled to receive platinum-based chemotherapy. Based on follow-up outcomes, 20 patients were classified as drug-resistant (DR) and 43 as drug-sensitive (non-DR). For survival analysis, patients were stratified into short-term (n = 25) and long-term (n = 38) survivor groups using the median OS (36 months) as the cutoff. Patients were randomly assigned to training and validation sets cohorts in an 8:2 ratio. Differentially hydroxymethylated regions (DhMRs) were identified using 5hmC-Seal sequencing and subjected to recursive feature elimination for feature selection. Logistic regression models were subsequently constructed. Model performance was evaluated and compared with conventional biomarkers, including CA125 and CA19-9.
resultsUsing a machine learning algorithm, eight 5hmC markers associated with platinum resistance were identified. In the validation set, the logistic model achieved a sensitivity of 75.0% and a specificity of 100.0% (AUC = 0.944). Eight 5hmC markers were identified for the prognosis prediction model, which achieved a sensitivity of 85.7% and a specificity of 80.0%, with an AUC of 0.914 in the validation set. The predictive performance of these models was superior to that of CA125 and CA19-9. Integration of the eight markers with CA125 and CA19-9 further improved predictive performance (AUC > 0.970). Downregulation of SLCO3A1 reversed cisplatin resistance, inhibited cell migration, and promoted cell proliferation, potentially via the Wnt/β-catenin signaling pathway.
conclusionOur results demonstrate that plasma cfDNA 5hmC signatures provide a minimally invasive epigenetic read-out for the preliminarily prediction of drug resistance and prognosis in patients with EOC. SLCO3A1 may represent a potential therapeutic target associated with platinum resistance and poor prognosis in EOC.
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