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

Abstract

Monitoring metabolic biomarkers could be utilized as an effective tool for the early detection of gastric cancer (GC) risk. We aimed to discover predictive serum biomarkers for GC and investigate biomarker-related metabolism. 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. Identifiedputative biomarkers were validated in baseline serum samples of 140 subjects (validation set; control and GC occurrence group, 70 each) using targeted metabolites analysis. 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. 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.