Untargeted Serum Metabolomics Reveals Differential Signatures in Gallstone-Associated and Gallstone-Free Gallbladder Cancer

Gallbladder cancer (GBC) is an aggressive malignancy often associated with gallstones (GBCGS), a condition distinct from gallstone disease (GSD). Both GBC and GBCGS are rare, with unclear pathogenesis and no established biomarker-based solutions. This pilot study aimed to identify distinct metabolic signatures in GBC and GBCGS for early diagnosis and stratification of high-risk GSD patients. A comparative untargeted serum metabolomic profiling was performed across three patient groups: GBC (n1=9), GBCGS (n2=11), and GSD (n3=10). A total of 35,385 mass-features in both positive and negative ionization modes with MS/MS characteristics were detected and annotated into 736 biochemicals.