Department of General Surgery, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Clinical Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Front Endocrinol (Lausanne). 2022 Nov 18;13:1039786. doi: 10.3389/fendo.2022.1039786. eCollection 2022.
Gastric cancer (GC) is a common lethal malignancy worldwide. Gastroscopy is an effective screening technique for decreasing mortality. However, there are still limited useful non-invasive markers for early detection of GC. Bile acids are important molecules for the modulation of energy metabolism. With an in-depth targeted method for accurate quantitation of 80 bile acids (BAs), we aimed to find potential biomarkers for the early screening of GC. A cohort with 280 participants was enrolled, including 113 GC, 22 benign gastric lesions (BGL) and 145 healthy controls. Potential markers were identified using a random forest machine algorithm in the discovery cohort (n=180), then validated in an internal validation cohort (n=78) and a group with 22 BGL. The results represented significant alterations in the circulating BA pool between GC and the controls. BAs also exhibited significant correlations with various clinical traits. Then, we developed a diagnostic panel that comprised six BAs or ratios for GC detection. The panel showed high accuracy for the diagnosis of GC with AUC of 1 (95%CI: 1.00-1.00) and 0.98 (95%CI: 0.93-1.00) in the discovery and validation cohort, respectively. This 6-BAs panel was also able to identify early GC with AUC of 1 (95%CI: 0.999-1.00) and 0.94 (95%CI: 0.83-1.00) in the discovery and validation cohort, respectively. Meanwhile, this panel achieved a good differential diagnosis between GC and BGL and the AUC was 0.873 (95%CI: 0.812-0.934). The alternations of serum bile acids are characteristic metabolic features of GC. Bile acids could be promising biomarkers for the early diagnosis of GC.
胃癌（GC）是全球常见的致命恶性肿瘤。胃镜检查是降低死亡率的有效筛查技术。然而，对于 GC 的早期检测，仍然缺乏有用的非侵入性标志物。胆汁酸是调节能量代谢的重要分子。我们采用一种深入的靶向方法，对 80 种胆汁酸（BA）进行准确定量，旨在寻找 GC 早期筛查的潜在生物标志物。共纳入 280 名参与者，包括 113 例 GC、22 例良性胃病变（BGL）和 145 例健康对照。在发现队列（n=180）中使用随机森林机器算法识别潜在标志物，然后在内部验证队列（n=78）和 22 例 BGL 组中进行验证。结果表明，GC 与对照组之间循环 BA 池存在显著变化。BA 还与各种临床特征显著相关。然后，我们开发了一个包含 6 种 BA 或比值的诊断面板，用于 GC 检测。该面板在发现和验证队列中用于 GC 诊断的 AUC 分别为 1（95%CI：1.00-1.00）和 0.98（95%CI：0.93-1.00），具有较高的准确性。该 6-BAs 面板还能够在发现和验证队列中分别以 AUC 为 1（95%CI：0.999-1.00）和 0.94（95%CI：0.83-1.00）识别早期 GC。同时，该面板能够很好地区分 GC 和 BGL，AUC 为 0.873（95%CI：0.812-0.934）。血清胆汁酸的变化是 GC 的特征代谢特征。胆汁酸可能是 GC 早期诊断的有前途的生物标志物。
