Associations of S-Adenosylmethionine and S-Adenosylhomocysteine with Hepatocellular Carcinoma

作者：Naana N. Yalley, Sebastian M. Armasu, Winnie Z. Fan, Irene K. Yan, Fowsiyo Ahmed, Per Stål, Lewis R. Roberts, Tushar Patel, Samuel O. Antwi · 发表于：Metabolites · 年份：2025 · DOI：10.3390/metabo15110740 · 被引用次数：4 · 研究领域：Folate and B Vitamins Research、Sulfur Compounds in Biology、Cancer Research and Treatments

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, increasingly arising in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Epigenetic dysregulation, particularly DNA methylation, has been implicated in MASLD-HCC development, yet the roles that the principal DNA methylation precursor metabolites, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), play in this association are unclear. Objective: We investigated associations of circulating SAM, SAH, the SAM/SAH ratio, with MASLD-HCC. Methods: In a multi-center pilot case–control study, we evaluated 69 MASLD-HCC cases and 136 cancer-free MASLD controls. Plasma SAM and SAH levels were quantified by liquid chromatography–tandem mass spectrometry. Metabolite levels were categorized as greater than or less than the median based on distribution in controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, sex, body mass index, smoking status, and type 2 diabetes. Results: MASLD-HCC cases had significantly higher plasma SAM levels (mean 121 vs. 96 nmol/L; p = 0.001) and SAM/SAH ratios (2.09 vs. 1.48; p = 6.42 × 10−7) than MASLD controls. In multivariable-adjusted models, elevated SAM levels (OR≥median vs. <median = 2.76; 95% CI: 1.38–5.72) and higher SAM/SAH ratio (OR≥median vs. <median = 2.30; 95% CI: 1.15–4.73) were associated with higher odds of MASLD-HCC. SAH alone was asso...