Department of Medicine, University of Louisville, Louisville, KY 40202, USA.
Hepatology and Nutrition, University of Louisville Division of Gastroenterology, Louisville, KY 40202, USA.
Int J Mol Sci. 2021 May 11;22(10):5093. doi: 10.3390/ijms22105093.
High-level occupational vinyl chloride (VC) exposures have been associated with hepatic hemangiosarcoma, which typically develops following a long latency period. Although VC is genotoxic, a more comprehensive mode of action has not been determined and diagnostic biomarkers have not been established. The purpose of this study is to address these knowledge gaps through plasma metabolomics.
Plasma samples from polyvinyl chloride polymerization workers who developed hemangiosarcoma (cases, = 15) and VC exposure-matched controls ( = 17) underwent metabolomic analysis. Random forest and bioinformatic analyses were performed.
Cases and controls had similar demographics and routine liver biochemistries. Mass spectroscopy identified 606 known metabolites. Random forest analysis had an 82% predictive accuracy for group classification. 60 metabolites were significantly increased and 44 were decreased vs. controls. Taurocholate, bradykinin and fibrin degradation product 2 were up-regulated by greater than 80-fold. The naturally occurring anti-angiogenic phenol, 4-hydroxybenzyl alcohol, was down-regulated 5-fold. Top affected ontologies involved: (i) metabolism of bile acids, taurine, cholesterol, fatty acids and amino acids; (ii) inflammation and oxidative stress; and (iii) nicotinic cholinergic signaling.
The plasma metabolome was differentially regulated in polyvinyl chloride workers who developed hepatic hemangiosarcoma. Ontologies potentially involved in hemangiosarcoma pathogenesis and candidate biomarkers were identified.
高水平职业性氯乙烯（VC）暴露与肝血管肉瘤相关，后者通常在较长潜伏期后发生。尽管 VC 具有遗传毒性，但尚未确定更全面的作用模式，也未建立诊断生物标志物。本研究旨在通过血浆代谢组学来解决这些知识空白。
对发生血管肉瘤（病例组，n=15）和 VC 暴露匹配对照组（n=17）的聚氯乙烯聚合工人的血浆样本进行代谢组学分析。进行随机森林和生物信息学分析。
病例组和对照组的人口统计学和常规肝功能生物化学特征相似。质谱鉴定出 606 种已知代谢物。随机森林分析对组分类的预测准确率为 82%。与对照组相比，有 60 种代谢物显著增加，44 种代谢物减少。牛磺胆酸盐、缓激肽和纤维蛋白降解产物 2 的上调幅度超过 80 倍。天然存在的抗血管生成酚 4-羟基苯甲醇下调 5 倍。受影响最大的本体论涉及：（i）胆汁酸、牛磺酸、胆固醇、脂肪酸和氨基酸的代谢；（ii）炎症和氧化应激；（iii）烟碱型胆碱能信号转导。
发生肝血管肉瘤的聚氯乙烯工人的血浆代谢组存在差异调节。确定了可能涉及血管肉瘤发病机制的本体论和候选生物标志物。
