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.
背景：胆囊癌是最常见的胆道恶性肿瘤，常于晚期确诊，部分原因在于缺乏可靠的生物标志物以及对非洲人群胆囊癌生物学特性的认知有限。本研究旨在描述非洲黑人血统胆囊癌患者的代谢组学和脂蛋白谱特征。方法：采用核磁共振波谱技术对血清样本进行分析。组间比较采用Wilcoxon检验，相关性分析采用Spearman秩检验，使用KODAMA算法进行无监督分析，通过偏最小二乘模型估算游离胆固醇与胆固醇酯比值，并采用多变量逻辑回归评估独立预测因子。结果：胆囊癌患者表现出乙醇水平改变和脂蛋白失调，包括中间密度脂蛋白胆固醇、中间密度脂蛋白甘油三酯和低密度脂蛋白甘油三酯升高，以及高密度脂蛋白胆固醇、高密度脂蛋白颗粒和中型高密度脂蛋白颗粒降低。总胆红素和结合胆红素与脂蛋白呈强相关性。无监督分析揭示了一个具有异常脂蛋白谱和游离胆固醇/胆固醇酯比值升高的胆囊癌亚组，提示存在胆汁淤积相关的脂蛋白X形成。天冬酰胺升高、乙醇降低及炎症代谢特征构成了胆囊癌的代谢指纹图谱。乙醇和胆红素被确定为胆囊癌的独立预测因子。结论：胆囊癌患者表现出独特的代谢组学和脂蛋白改变，这些改变可能是疾病进展的基础，并可作为潜在的生物标志物。这些发现增进了对非洲人群胆囊癌病理生理学的理解，可能为未来的诊断策略提供参考。
肿瘤(癌症)患者之家