Urinary Metabolic Profile and the Development of HBV- Related Hepatocellular Carcinoma: Prospective Study
Date Issued
2015
Date
2015
Author(s)
Huang, Yu-Kang
Abstract
Background: Metabolomics is the final downstream product of metabolism. Metabolomics alternations represent the aberrant of physiology, thus metabolomics plays a major role of early detection and diagnosis of cancer development. Present study focus on long term follow-up hepatitis B virus (HBV) carriers who are the high risk population of hepatocellular carcinoma (HCC). Investigating the relationship between metabolites and HCC through metabolomics analytic techniques enable to discover the potential biomarkers for predicting HCC risk. Materials and methods: Study subjects were obtained from a cohort of 5364 men aged over 30, including 355 HBV carriers and 98 non-carriers. During the first stage, we examined the difference of metabolites in HBV carriers and non-carriers group. Further, a nested case-control study design was conducted for HBV carriers, 170 HCC cases occurred during the follow-up. We matched control group for HCC among HBV carriers by age and beginning time of recruitment. Nuclear magnetic resonance (NMR) was applied to detect metabolites in urine samples. Wilcoxon rank test was used to perform univariate analysis. Those metabolites which significantly related to HCC were subsequently divided into five groups according to quintile cutoff points and Mantel–Haenszel was used to determine the trend of increasing quintile level. Finally, logistic regression model was adopted to compare the dose-response of metabolites before and after adjusting confounders. Results: A total of 24 metabolites was identified, 4 metabolites (3-aminoisobutyrate, N-methylhydantoin, glycine, creatinine) were positively correlated to HBsAg status but no statistical significance with HCC. Three metabolites (N-phenylacetylglycine, hypoxanthine, tropate) were found positively associated with HBsAg status while inversely associated with HCC. Three metabolites (citrate, taurine and trimethylamine N-oxide) were found related to HCC and were selected to further statistical analysis. According to quintile levels of three urinary metabolites, we found positive dose-response in citrate while decreasing trend was found in other two metabolites but represent a U-shape association. The result remain the same after adjustment of potential confounders. Conclusion: We found changes in metabolite profiles during transition from healthy HBV carrier status to HCC. Citrate has positive association with HCC for certain. Taurine and trimethylamine N-oxide have negative association but the U-shape relationship require a further confirmation by independent research.
Subjects
urinary metabolomics
hepatitis B virus
hepatocellular carcinoma
SDGs
Type
thesis
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