Biomarker Discovery for Hepatocellular Carcinoma in Patients with Liver Cirrhosis Using Untargeted Metabolomics and Lipidomics Studies.

Biomarker Discovery for Hepatocellular Carcinoma in Patients with Liver Cirrhosis Using Untargeted Metabolomics and Lipidomics Studies.
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DOI:
10.3390/metabo13101047
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发表时间:
2023-10-02
期刊:
影响因子:
4.1
通讯作者:
Ressom HW
Ressom HW
中科院分区:
生物学3区
文献类型:
--
作者:
Rashid MM;Varghese RS;Ding Y;Ressom HW

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肝细胞癌(HCC)是最常见的肝癌类型,是全球第三大死亡原因。肝细胞癌患者预后较差,因为症状通常在疾病晚期才出现。此外,传统生物标志物在早期识别肝细胞癌时效果欠佳,这增加了寻找新的更有效生物标志物的需求。本研究利用代谢组学和脂质组学方法,旨在识别用于肝硬化(LC)患者肝细胞癌诊断的血清生物标志物。使用超高效液相色谱 - Q Exactive质谱仪(UHPLC - Q - Exactive - MS)对20例肝细胞癌病例和20例肝硬化患者的血清样本进行了分析。识别出了肝细胞癌病例和肝硬化患者之间显著改变的代谢物和脂质,包括有机酸、氨基酸、三羧酸循环中间体、脂肪酸、胆汁酸、甘油磷脂、鞘脂和甘油酯。在胆汁酸、脂肪酸和甘油磷脂的浓度方面观察到最显著的差异。在肝细胞癌病例中,磷脂酰乙醇胺和甘油三酯水平显著升高,而脂肪酸和磷脂酰胆碱水平则大幅下降。此外,观察到所有已识别的代谢物在受试者工作特征(ROC)曲线下面积均优于甲胎蛋白(AFP)。对这些代谢物的通路分析显示,脂肪酸、脂质和能量代谢是受影响最大的通路。本研究中识别出的潜在生物标志物将在未来研究中通过靶向定量进行验证。
Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is the third leading cause of mortality globally. Patients with HCC have a poor prognosis due to the fact that the emergence of symptoms typically occurs at a late stage of the disease. In addition, conventional biomarkers perform suboptimally when identifying HCC in its early stages, heightening the need for the identification of new and more effective biomarkers. Using metabolomics and lipidomics approaches, this study aims to identify serum biomarkers for identification of HCC in patients with liver cirrhosis (LC). Serum samples from 20 HCC cases and 20 patients with LC were analyzed using ultra-high-performance liquid chromatography-Q Exactive mass spectrometry (UHPLC-Q-Exactive-MS). Metabolites and lipids that are significantly altered between HCC cases and patients with LC were identified. These include organic acids, amino acids, TCA cycle intermediates, fatty acids, bile acids, glycerophospholipids, sphingolipids, and glycerolipids. The most significant variability was observed in the concentrations of bile acids, fatty acids, and glycerophospholipids. In the context of HCC cases, there was a notable increase in the levels of phosphatidylethanolamine and triglycerides, but the levels of fatty acids and phosphatidylcholine exhibited a substantial decrease. In addition, it was observed that all of the identified metabolites exhibited a superior area under the receiver operating characteristic (ROC) curve in comparison to alpha-fetoprotein (AFP). The pathway analysis of these metabolites revealed fatty acid, lipid, and energy metabolism as the most impacted pathways. Putative biomarkers identified in this study will be validated in future studies via targeted quantification.
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