Metabolic Reprogramming in Retinoblastoma Patients: Treatment Naïve Active Retinoblastoma Versus Regressed Tumors Post-Treatment.

Purpose: The purpose of this study was to explore and compare the serum metabolic alterations in treatment-naïve active retinoblastoma (RB) and regressed RB post-treatment. Methods: Analysis of serum metabolites in six patients with RB before, during, and after completion of treatment and their comparison with six age-matched controls. Serum metabolomics was performed by using 1H nuclear magnetic resonance (NMR) spectroscopy. Results: Serum metabolomics yielded 70 metabolites, including amino acids, carbohydrates, and organic acids, in patients with RB and healthy controls. Distinct serum metabolite clusters were noted in the PLSDA model for controls, patients with treatment-naïve active RB (AR), and patients with regressed tumors post-treatment (RT). Statistical analysis of metabolic profiles revealed a change in serum metabolite profiles in patients with RT compared with patients with AR. Several metabolites that were up- or downregulated in patients with RT were the intermediates of glycolysis, the tricarboxylic acid (TCA) cycle, and the membrane synthesis pathway. It has been observed that a few metabolites, such as GABA, aspartate, biotin, methionine, arginine, creatine, and lactate, which were upregulated in patients with AR with respect to controls, were suppressed in patients with RT. Additionally, monitoring the concentration of specific metabolites in patients with RB after each treatment cycle revealed that all treated patients with RB and with RT have a similar pattern of increase/decrease of metabolites with respect to their concentrations compared with their AT counterparts. However, they have followed distinct trajectories based on the status of the tumor during treatment cycle. Conclusions: The serum metabolic profile changes based on tumor status (active versus regressed). Serum metabolites may serve as a prognostic biomarker suggestive of tumor activity and response to treatment.