Background: Gall bladder cancer (GBC) is the most common biliary tract malignancy and is often diagnosed at advanced stages, partly due to the absence of reliable biomarkers and limited understanding of its biology in African populations. This study aimed to characterize the metabolomic and lipoprotein profiles of GBC patients of Black African ancestry. Methods: NMR spectroscopy was used to profile the serum samples. Group comparisons used Wilcoxon tests, correlations used Spearman’s rank test, unsupervised analysis was carried out using the KODAMA algorithm, partial least squares modeling estimated free cholesterol (FC) to cholesterol ester (CE) ratios, while multivariate logistic regression evaluated independent predictors. Results: GBC patients showed altered ethanol levels and dysregulated lipoproteins, including increased IDL-C, IDL-TG, and LDL-TG, and decreased HDL-C, HDL-P, and medium HDL-P. Total and conjugated bilirubin strongly correlated with lipoproteins. Unsupervised analysis revealed a GBC subgroup with abnormal lipoprotein profiles and elevated FC/CE ratios, suggesting cholestasis-related LpX formation. Elevated asparagine, reduced ethanol, and an inflammatory metabolic signature characterized the GBC fingerprint. Ethanol and bilirubin emerged as independent predictors of GBC. Conclusions: GBC patients exhibit distinct metabolomic and lipoprotein alterations that may underlie disease progression and serve as potential biomarkers. These findings enhance understanding of GBC pathophysiology in African populations and may inform future diagnostic strategies.

Background Gall bladder cancer (GBC) is the most prevalent cancer of the biliary tract with a poor prognosis. Most of the patients are diagnosed at an advanced stage. This is due to a lack of reliable biomarkers and an understanding of the tumour biology in our patient population. This study aims to demonstrate the metabolomic and lipoprotein profiles associated with GBC patients of African ancestry. Methods: An untargeted metabolomics analysis was conducted on serum obtained from consenting individuals (41 GBC and 29 Benign Biliary Pathology (BBP)). Statisti-cal analysis was conducted in R (v 4.3.2), and Wilcoxon tests were used to compare the groups. Spearman’s rank test was used for correlation analyses. Unsupervised analysis of the groups was carried out using the KODAMA algorithm. Results: GBC patients showed a significant alteration of the metabolite ethanol as well as lipoproteins such as IDL-C, IDL-TG, LDL-TG, compared to BBP patients. In contrast, decreased levels of HDL-C, HDL-P, medium HDL-P were observed in GBC patients. Both Total and conjugated bilirubin levels showed a strong correlation with lipopro-teins. Furthermore, the altered free cholesterol to cholesterol ester ratio was demon-strated to be linked to abnormal lipid metabolism. Conclusion: This study demonstrated alterations in key lipoproteins and metabolites in the patient population. These alterations may play a role in disease progression and potentially serve as novel biomarkers for the disease.