{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:15:06Z","timestamp":1785237306487,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,6]],"date-time":"2025-09-06T00:00:00Z","timestamp":1757116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"South African Medical Research Council"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/cancers17172925","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T10:29:07Z","timestamp":1757327347000},"page":"2925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Distinct Metabolomic and Lipoprotein Signatures in Gall Bladder Cancer Patients of Black African Ancestry"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7526-9985","authenticated-orcid":false,"given":"John","family":"Devar","sequence":"first","affiliation":[{"name":"Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa"},{"name":"Hepatopancreatobiliary Unit, Department of Surgery, Chris Hani-Baragwanath Academic Hospital, Soweto, Johannesburg 1864, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9368-9166","authenticated-orcid":false,"given":"Nnenna","family":"Elebo","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa"},{"name":"Bioinformatics Unit, International Centre for Genetic Engineering and Biotechnology, Observatory, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashna","family":"Makan","sequence":"additional","affiliation":[{"name":"Wits Donald Gordon Medical Centre, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Pincus","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5996-2712","authenticated-orcid":false,"given":"Nicola","family":"Lahoud","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7052-7156","authenticated-orcid":false,"given":"Stefano","family":"Cacciatore","sequence":"additional","affiliation":[{"name":"Bioinformatics Unit, International Centre for Genetic Engineering and Biotechnology, Observatory, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Candy","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4026-1697","authenticated-orcid":false,"given":"Ekene Emmanuel","family":"Nweke","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa"},{"name":"Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Florida, Roodepoort 1709, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,6]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA A Cancer J. 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