High serum levels of l-carnitine and citric acid negatively correlated with alkaline phosphatase are detectable in Koreans before gastric cancer onset

Introduction: Monitoring metabolic biomarkers could be utilized as an effective tool for the early detection of gastric cancer (GC) risk. Objective: We aimed to discover predictive serum biomarkers for GC and investigate biomarker-related metabolism. Methods: Subjects were randomly selected from the Korean Cancer Prevention Study-II cohort and matched by age and sex. We analyzed baseline serum samples of 160 subjects (discovery set; control and GC occurrence group, 80 each) via nontargeted screening. Identified putative biomarkers were validated in baseline serum samples of 140 subjects (validation set; control and GC occurrence group, 70 each) using targeted metabolites analysis. Results: The final analysis was conducted on the discovery set (control, n = 52 vs. GC occurrence, n = 50) and the validation set (control, n = 43 vs. GC occurrence, n = 44) applying exclusion conditions. Eighteen putative metabolite sets differed between two groups found on nontargeted metabolic screening. We focused on fatty acid-related energy metabolism. In targeted analysis, levels of decanoyl-l-carnitine (p = 0.019), l-carnitine (p = 0.033), and citric acid (p = 0.025) were significantly lower in the GC occurrence group, even after adjusting for age, sex, and smoking status. Additionally, l-carnitine and citric acid were confirmed to have an independently significant relationship to GC development. Notably, alkaline phosphatase showed a significant correlation with these two biomarkers. Conclusion: Changes in serum l-carnitine and citric acid levels that may result from alterations of fatty-acid-related energy metabolism are expected to be valuable biomarkers for the early diagnosis of GC risk.