NMR-Based Lipid Metabolite Profiles to Predict Outcomes in Patients Undergoing Interventional Therapy for a Hepatocellular Carcinoma (HCC): A Substudy of the SORAMIC Trial

SIMPLE SUMMARY: A hepatocellular carcinoma (HCC) is the most common cause of death in patients suffering from chronic liver diseases. In order to improve the prediction of outcomes in HCC patients, there is a need for new biomarkers. This pilot study aimed at identifying serum metabolites for the prediction of outcomes of HCC patients using nuclear magnetic resonance (NMR) spectroscopy. This analysis revealed that high serum concentrations of myo-inositol or dimethylamine were associated with an improved overall survival. In contrast, high concentrations of total cholesterol, LDL-cholesterol and LDL particles (LDL-P) were associated with a decreased overall survival. The identification of novel biomarkers using this NMR-based technology holds promise for opening new directions in the conduction of interventional trials in HCCs. ABSTRACT: Background: This exploratory study aimed to evaluate lipidomic and metabolomic profiles in patients with early and advanced HCCs and to investigate whether certain metabolic parameters may predict the overall survival in these patients. Methods: A total of 60 patients from the prospective, randomized-controlled, multicenter phase II SORAMIC trial were included in this substudy; among them were 30 patients with an early HCC who underwent radiofrequency ablation combined with sorafenib or a placebo and 30 patients with an advanced HCC who were treated with a selective internal radiation therapy (SIRT) plus sorafenib vs. sorafenib alone. The blood serum of these patients was analyzed using a standardized nuclear magnetic resonance (NMR) platform. All tested metabolites were correlated with the overall survival. Results: The overall survival (OS) was significantly higher in patients with an early HCC (median OS: 34.0 months) compared with patients with an advanced HCC (median OS: 12.0 months) (p < 0.0001). Patients with high serum concentrations of myo-inositol (MI) had a higher overall survival compared with patients with low concentrations (21.6 vs. 13.8 months) with a Pearson correlation coefficient of 0.331 (p = 0.011). Patients with high serum concentrations of dimethylamine had a higher overall survival compared with patients with low concentrations (25.1 vs. 19.7 months) with a Pearson correlation coefficient of 0.279 (p = 0.034). High concentrations of total cholesterol, LDL-cholesterol and LDL particles (LDL-P) were associated with a decreased overall survival. Conclusions: NMR-based lipidomic and metabolomic profiling has the potential to identify individual metabolite biomarkers that predict the outcome of patients with an HCC exposed to non-invasive therapeutic management.