Abstract
BackgroundHigher choline and betaine levels have been linked to lower risk of liver cancer, whereas existing data in relation to hepatocellular carcinoma (HCC) prognosis are scarce. Our objective was to examine the associations of the serum choline and betaine with HCC survival.Methods866 newly diagnosed HCC patients were enrolled in the Guangdong Liver Cancer Cohort. Serum choline and betaine were assessed using high-performance liquid chromatography with online electro-spray ionization tandem mass spectrometry. Liver cancer-specific survival (LCSS) and overall survival (OS) were calculated. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsSerum choline levels were associated with better LCSS (T3 vs. T1: HR = 0.69, 95% CI: 0.51–0.94; P-trend < 0.05) and OS (T3 vs. T1: HR = 0.73, 95% CI: 0.54–0.99; P-trend < 0.05). The associations were significantly modified by C-reactive protein (CRP) levels but not by other selected prognostic factors including sex, age, etc. The favorable associations between serum choline and LCSS and OS were only existed among patients with CRP ≥3.0 mg/L. No significant associations were found between serum betaine levels and either LCSS or OS.ConclusionsThis study revealed that higher serum choline levels were associated with better HCC survival, especially in HCC patients with systemic inflammation status. No significant associations were found between serum betaine and HCC survival. Our findings suggest the benefits of choline on HCC survival.Trial registrationThe Guangdong Liver Cancer Cohort was registered at clinicaltrials.gov as NCT03297255.
Highlights
Higher choline and betaine levels have been linked to lower risk of liver cancer, whereas existing data in relation to hepatocellular carcinoma (HCC) prognosis are scarce
Choline is a major source of methyl groups via oxidation to betaine, their functions involving the re-methylation of homocysteine to methionine are critical for DNA and histone methylation homeostasis, and have been reported to be associated with cancer risk [2] and survival [7,8,9,10]
Experimental studies have reported that when deprived of choline, varying degrees of liver damage and liver diseases developed, including elevated transaminases [11], affected lipid metabolism and transport [12], fatty liver [13], liver cirrhosis [13] and even liver cancer [14], whereas choline or betaine supplementation ameliorated liver damage [15, 16], and choline supplementation increased global DNA methylation and DNA methyltransferase expression in HepG2 cells [17], which implied that choline or betaine might be associated with hepatocarcinogenesis, and with liver cancer survival
Summary
Higher choline and betaine levels have been linked to lower risk of liver cancer, whereas existing data in relation to hepatocellular carcinoma (HCC) prognosis are scarce. Choline is a major source of methyl groups via oxidation to betaine, their functions involving the re-methylation of homocysteine to methionine are critical for DNA and histone methylation homeostasis, and have been reported to be associated with cancer risk [2] (including liver cancer) and survival [7,8,9,10]. No existing studies have reported the associations between choline and betaine and liver cancer survival, it would be a very meaningful topic to investigate the influence of choline and betaine status on HCC prognosis in Chinese population
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