Integrated NMR-Based Metabolomics and Clinical Profiling for Differential Diagnosis of Gallbladder Cancer and Gallstone Disease.

Background:
Differentiating gallbladder cancer (GBC) from gallstone disease (GSD) remains a significant clinical challenge due to overlapping clinical manifestations and the limited diagnostic accuracy of conventional clinical parameters. This study aimed to evaluate the diagnostic utility of serum ¹H NMR-based metabolomics integrated with clinical profiling for improved differentiation between GBC and GSD.

Methods:
Serum samples were collected from 50 patients with GBC, 50 patients with GSD, and 20 healthy controls. Metabolic profiling was performed using ¹H Nuclear Magnetic Resonance (NMR) spectroscopy. Differential metabolites were identified by comparing GBC and GSD metabolic profiles. Metabolomic and clinical datasets were subsequently integrated using Multi-Omics Factor Analysis (MOFA) to assess their relative contribution to disease classification and diagnostic performance.

Results:
Comparative metabolomic analysis revealed significant downregulation of β-glucose, alanine, and carnitine in GBC compared with GSD. MOFA-based integration demonstrated that the metabolomic dataset contributed more strongly to disease discrimination than clinical parameters alone, indicating superior diagnostic performance of NMR-derived metabolic signatures for differentiating GBC from GSD.

Conclusion:
Integrated analysis of ¹H NMR-based metabolomics and clinical profiling highlights the superior diagnostic potential of metabolomic biomarkers over conventional clinical parameters for distinguishing GBC from GSD. These findings support the application of NMR-based metabolomics as a promising complementary tool for the early and accurate differential diagnosis of gallbladder diseases.