Objectives: In the prospective Korean Cancer Prevention Study-II (KCPS-II), we investigated the application of metabolomics to differentiate subjects with incident liver cirrhosis (LC group) from subjects who remained free of LC (control group) during a mean follow-up period of 7 years, with the aim of identifying valuable biomarkers for LC.
Methods: Metabolic alterations were investigated using baseline serum samples from 94 subjects with incident LC and 180 age- and sex-matched LC-free subjects via ultra-performance liquid chromatography (UPLC)-linear-trap quardrupole (LTQ)-Orbitrap mass spectrometry (MS).
Results: A total of 46 metabolites were identified through the metabolic analysis. Among them, 11 metabolite levels were significantly higher, and 18 metabolite levels were significantly lower in the LC group than in the control group. 9 metabolic pathways, including glyoxylate and dicarboxylate metabolism, amino acid metabolism, fatty acid metabolism, linoleic acid metabolism, α-linolenic acid metabolism, and arachidonic acid metabolism, showed significant differences between the two groups. Logistic regression revealed that the incidence of LC was independently affected by serum levels of myristic acid, palmitic acid, linoleic acid, eicosapentaenoic acid (EPA), lysophosphatidic acid (LPA) (18:1), glycolic acid, lysophosphatidylcholine (lysoPC) (22:6), and succinylacetone (R2=0.837, P<0.001).
Conclusions: This prospective study showed the clinical relevance of dysregulation of various metabolisms on the incidence of LC. Additionally, myristic acid, palmitic acid, linoleic acid, EPA, LPA (18:1), glycolic acid, lysoPC (22:6), and succinylacetone were identified as independent variables affecting the incidence of LC.
H. Yoo: None. M. Kim: None. Y. Han: None. C. Yoonjeong: None. J. Lee: None.
Korean Ministry of Health and Welfare (HI14C2686); Korean National Research Foundation (NRF-2012M3A9C4048762, NRF-2017R1C1B2007195)