Metabolomics Plasma Biomarkers Associated with the HRD Phenotype in Ovarian Cancer

<b>Background</b>: Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies due to its often-late diagnosis and complex molecular heterogeneity. Understanding the metabolic alterations in OC can provide insights into its pathophysiology and potential therapeutic targets. This study aimed to explore serum metabolomic profiles and their correlation with clinical and pathological features in OC patients. <b>Materials and Methods</b>: Thirty serum samples were collected from patients diagnosed with ovarian tumors (OTs) (n = 24 malignant, n = 6 benign) and undergoing treatment at Careggi University Hospital. Additionally, 47 samples were obtained from age-matched healthy female donors. Serum samples underwent processing and analysis using an H-NMR (Nuclear Magnetic Resonance) platform to identify a panel of metabolites. Correlation analysis between the metabolomic data and clinical parameters was performed using R software (v.4.4.0). <b>Results</b>: Differential metabolomic profiling showed a significant upregulation of metabolites associated with the purine salvage pathway (i.e., hypoxanthine and inosine) and the ketone bodies axis (i.e., acetone, 3-hydroxybutyrate, and acetate) in samples from ovarian tumor (OT) patients compared to healthy donors. Within malignant OC samples, metabolomic profiles significantly correlated with BRCA1/2 mutation status (BRCA1/2-mutated vs. wild-type) and homologous recombination deficiency (HRD) status. <b>Conclusions</b>: The analysis revealed significant variation in specific metabolites such as betaine, creatinine, carnitine, glycerol, and mannose; notably, a downregulation of these metabolites was observed in HRD-positive patients. The study identifies significant metabolomic alterations in OC, implicating pathways such as purine salvage and ketone bodies. Intriguingly, consistent variation in specific metabolites across BRCA/HRD phenotypes underscores their potential as OC biomarkers. Further research is needed to validate these findings and explore their prognostic and therapeutic implications.