Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: Findings from a prospective cohort study

Abstract

Perturbations in levels of amino acids (AA) and their derivatives are observed in hepatocellular carcinoma (HCC). Yet, it is unclear whether these alterations precede or are a consequence of the disease, nor whether they pertain to anatomically related cancers of the intrahepatic bile duct (IHBC), and gallbladder and extrahepatic biliary tract (GBTC). Circulating standard AA, biogenic amines and hexoses were measured (Biocrates AbsoluteIDQ-p180Kit) in a case-control study nested within a large prospective cohort (147 HCC, 43 IHBC and 134 GBTC cases). Liver function and hepatitis status biomarkers were determined separately. Multivariable conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI) for log-transformed standardised (mean = 0, SD = 1) serum metabolite levels and relevant ratios in relation to HCC, IHBC or GBTC risk. Fourteen metabolites were significantly associated with HCC risk, of which seven metabolites and four ratios were the strongest predictors in continuous models. Leucine, lysine, glutamine and the ratio of branched chain to aromatic AA (Fischer's ratio) were inversely, while phenylalanine, tyrosine and their ratio, glutamate, glutamate/glutamine ratio, kynurenine and its ratio to tryptophan were positively associated with HCC risk. Confounding by hepatitis status and liver enzyme levels was observed. For the other cancers no significant associations were observed. In conclusion, imbalances of specific AA and biogenic amines may be involved in HCC development

Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study

“…The present analysis included existing biomarker data for the same set of cases and matched controls [2, 7, 9]. For a total of 100 of the HCC cases (those diagnosed before 2006) and their matched controls, existing data were available for HBV/HCV seropositivity (ARCHITECT HBsAg and anti-HCV chemiluminescent microparticle immunoassays; Abbott Diagnostics, France) and biomarkers of hepatic injury (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [GGT], liver-specific alkaline phosphatase [AP], albumin, total bilirubin, and total protein; ARCHITECT c Systems™; Abbott Diagnostics) [2].…”

“…Recent observations from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort also show a role for dietary and lifestyle exposures in HCC development [2–6] and indicate metabolic differences between cases and controls [7–9]. Other observations suggest that many of these same factors can weaken the colonic epithelial barrier function [10–12], allowing the translocation of toxic bacterial products such as lipopolysaccharide (LPS; also known as endotoxin, an integral part of the outer membrane of Gram-negative bacterial cell walls) and flagellin (the primary structural component of flagella).…”

Lipid Metabolism in Liver Cancer

“…As same Lipid Metabolism in Liver Cancer http://dx.doi.org/10.5772/64993as the intermediate liver diseases, HCC maintained the aforementioned "core metabolic phenotype" of bile acid and phospholipid perturbation [66,71,[73][74][75]. Some findings also demonstrated similar liver impairments of ammonium detoxication and amino acid metabolism in HCC as in cirrhosis [66,72,73,76].…”

Redefining environmental exposure for disease etiology

“…Table 1 summarizes results from 13 studies that measured small molecules in plasma or serum from incident cases and controls to discover possible causes of cardiovascular disease, 38 diabetes, 39–43 and a host of cancers. 44–52 Periods of follow-up ranged from 2 to 9.6 years and 10 of the 14 studies were performed with LC-MS. Interestingly, only three of the LC-MS studies employed untargeted designs 38,50,51 and thus many did not take full advantage of the omics capabilities of the analytical platforms. Nonetheless, these studies demonstrate that metabolomics can readily characterize complex mixtures of small molecules in a few microliters of archived blood from incident cases and matched controls.…”