Distinct Metabolomic and Lipoprotein Signatures in Gallbladder Cancer Patients of African Ancestry

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Abstract
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.
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