Metabolomics study identified bile acids as potential biomarkers for gastric cancer: A case control study

Abstract

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.

Alteration of gastric microbiota and transcriptome in a rat with gastric intestinal metaplasia induced by deoxycholic acid

“…Li et al designed a case–control study in a Chinese population and found that the serum total BA >10 μmol/L can be a diagnostic threshold for the risk of gastrointestinal cancer, especially for the risk of esophageal cancer and GC (Li et al, 2022b ). The latest clinical research (Pan et al, 2022 ) presented clearly promoted conjugated and unconjugated BAs in the sera of patients with GC, again showing that serum BAs participate in the development of gastric carcinogenesis apart from GIM. The present transcriptome of the gastric mucosa showed that the overexpression levels of GIM-related genes were consistent with those in the previous reports, such as Cdx2, Nr1h4 , and Cdh17 .…”

Reprogramming of regulatory T cells in inflammatory tumor microenvironment: can it become immunotherapy turning point?

“…In targeted Tregs reprogramming, multi-omics approaches combined with novel computational tools can be applied to target various signals and molecules on Tregs ( 243 – 245 ). It enables a better understanding of the gene regulatory networks regulating Treg function, as well as the identification of additional biomarkers that define Tregs function in the TME.…”

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis

“…Previously, bile reflux has been shown to be an independent risk factor for precancerous gastric lesions and GC (Zhang et al 2021 ). Especially, HCA a primary bile acid and HDCA, a secondary bile acid, play a crucial role in regulating energy expenditure and were both identified to be decreased in patients with UGC (Pan et al 2022 ). However, our results are inconsistent with previous literature as multiple authors described primary bile acids to be reduced and secondary bile acids to be increased in patients with UGC (Rezen et al 2022 ).…”