Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma.
Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma.
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DOI：
10.1038/srep18175
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发表时间：
2015-12-10
影响因子：
4.6
通讯作者：
Yan X
中科院分区：
文献类型：
--
作者：
Gao R;Cheng J;Fan C;Shi X;Cao Y;Sun B;Ding H;Hu C;Dong F;Yan X
肝细胞癌（HCC）是一种常见的恶性肿瘤，具有区域特异性病因。不幸的是，85%的肝癌病例是在晚期被诊断出来的。为了降低死亡率和治疗费用，迫切需要可靠的肝癌早期诊断生物标志物。我们建立了一种非靶向的气相色谱-飞行时间-质谱（GC-TOFMS）代谢组学方法，并结合随机森林（RF）分析，对201例健康对照（NC）、B肝炎病毒（HBV）、肝硬化（LC）和肝癌患者的血清样本进行分析，以探讨肝细胞癌发生发展过程中的代谢特征。最终，确定了15种代谢产物与该过程密切相关。苯丙氨酸、苹果酸和5-甲氧基色胺用于HBV与NC，棕榈酸用于LC与HBV，天冬酰胺和β-谷氨酸用于HCC与LC被筛选为具有优异判别性能的肝脏疾病特异性潜在生物标志物。这些肝脏疾病中的所有代谢紊乱都与能量代谢、大分子合成和维持氧化还原平衡以保护肿瘤细胞免受氧化应激的途径有关。
Hepatocellular carcinoma (HCC) is a common malignancy that has region specific etiologies. Unfortunately, 85% of cases of HCC are diagnosed at an advanced stage. Reliable biomarkers for the early diagnosis of HCC are urgently required to reduced mortality and therapeutic expenditure. We established a non-targeted gas chromatography–time of flight–mass spectrometry (GC-TOFMS) metabolomics method in conjunction with Random Forests (RF) analysis based on 201 serum samples from healthy controls (NC), hepatitis B virus (HBV), liver cirrhosis (LC) and HCC patients to explore the metabolic characteristics in the progression of hepatocellular carcinogenesis. Ultimately, 15 metabolites were identified intimately associated with the process. Phenylalanine, malic acid and 5-methoxytryptamine for HBV vs. NC, palmitic acid for LC vs. HBV, and asparagine and β-glutamate for HCC vs. LC were screened as the liver disease-specific potential biomarkers with an excellent discriminant performance. All the metabolic perturbations in these liver diseases are associated with pathways for energy metabolism, macromolecular synthesis, and maintaining the redox balance to protect tumor cells from oxidative stress.