代谢物谱的纵向变化及其与乙型肝炎相关肝细胞癌发生风险

StephenW

Longitudinal change of metabolite profile and its relation to multiple risk factors for the risk of developing hepatitis B-related hepatocellular carcinoma

    September 2020Molecular Carcinogenesis

    DOI: 10.1002/mc.23255

    Bo-Yuan HuangMin-Ru TsaiJia-Kai Hsu

    Ming-Whei YuMing-Whei Yu


Abstract
Despite considerable knowledge of viral pathogenesis, the pathophysiological changes related to the multifactorial, multistep process of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) development remains unclear. Longitudinal metabolomics study can reveal biological process for disease progression. We performed metabolite profiling with longitudinal prediagnostic plasma samples from two nested case-control studies of hepatitis B surface antigen carriers participating in ultrasound screening for HCC, one within a government employee cohort (870 samples from 109 HCC cases and 107 controls) and the other within a hospital-based cohort (266 samples from 63 HCC cases and 114 controls). Of the 34 measured metabolites, tyrosine, isoleucine, and glutamine were consistently associated with HCC. In analyses combining longitudinal data, a high metabolic risk score based on the three amino acids was robustly associated with increased risk of HCC (OR = 3.71, 95% confidence interval: 2.53-5.42), even after adjustment for clinical factors, or when assessed for different times up to ≥8 years before diagnosis. Similar association was observed in an independent, prospective analysis comprising 633 randomly selected individuals of the government employee cohort. More importantly, this metabolite signature was longitudinally influenced by HBV-infection phase and involved in gradual progression to liver fibrosis and cirrhosis. Furthermore, mediation analysis showed that the score mediated substantial proportions of the associations of key viral factors, insulin resistance, and diabetes status with HCC risk. Our results suggest that an amino-acid dysregulation metabotype may play a role in HBV-related HCC development, and may also be linked to common pathways that mediate increased HCC risks.

StephenW

代谢物谱的纵向变化及其与乙型肝炎相关肝细胞癌发生风险的多种危险因素的关系

    2020年9月分子致癌

    DOI：10.1002 / mc.23255

    蔡伯凯黄伯如蔡家凯

    于明惠于明惠


抽象
尽管对病毒的发病机理有相当多的了解，但与乙型肝炎病毒（HBV）相关的肝细胞癌（HCC）发育的多因素，多步骤过程相关的病理生理变化仍不清楚。纵向代谢组学研究可以揭示疾病进展的生物学过程。我们对来自两项嵌套的参与肝癌超声筛查的乙肝表面抗原携带者的病例对照研究进行了纵向诊断前血浆样品的代谢物分析，其中一项在政府雇员队列中进行（一项在109名HCC病例和107名对照中进行了870例）医院为基础的队列研究（来自63例HCC病例和114例对照的266个样本）。在34种测定的代谢产物中，酪氨酸，异亮氨酸和谷氨酰胺始终与HCC相关。在结合纵向数据的分析中，即使经过临床因素调整或评估后，基于这三种氨基酸的高代谢风险评分也与肝癌风险增加密切相关（OR = 3.71，95％置信区间：2.53-5.42）在诊断之前≥8年的不同时间。在一项独立的前瞻性分析中，观察到相似的关联，该分析包括633名政府雇员的随机选择的个人。更重要的是，这种代谢物特征在纵向上受到HBV感染期的影响，并逐渐发展为肝纤维化和肝硬化。此外，调解分析表明，该得分介导了关键比例的关键病毒因素，胰岛素抵抗和糖尿病状态与HCC风险之间的关联。我们的结果表明，氨基酸失调代谢型可能在HBV相关的HCC