1H-NMR Based Serum Metabolomics Highlights Different Specific Biomarkers between Early and Advanced Hepatocellular Carcinoma Stages
1H-NMR Based Serum Metabolomics Highlights Different Specific Biomarkers between Early and Advanced Hepatocellular Carcinoma Stages
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DOI：
10.3390/cancers12010241
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发表时间：
2020-01-01
期刊：
影响因子：
5.2
通讯作者：
Giudetti, Anna Maria
中科院分区：
文献类型：
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作者：
Casadei-Gardini, Andrea;Del Coco, Laura;Giudetti, Anna Maria
非靶向血清代谢组学分析的应用代表了一种非侵入性的工具，可以识别新的临床生物标志物，提供早期诊断鉴别，并深入了解肝细胞癌(HCC)进展的病理机制。在这项研究中，我们使用质子核磁共振波谱和多变量数据分析来描述早期(n=28)和晚期(n=36)肝癌患者的血清代谢组。我们发现，H-1-核磁共振代谢组学分析可以区分早期和晚期肝细胞癌患者，交叉验证的准确率接近100%。正交偏最小二乘判别分析显示，晚期与早期肝细胞癌患者的血糖、乳酸、血脂及部分氨基酸如丙氨酸、谷氨酰胺、1-甲基组氨酸、赖氨酸和缬氨酸水平均有显著变化。此外，在早期肝细胞癌患者中，Kaplan-Meier分析强调血清酪氨酸水平是总生存期(OS)的预测因子。总体而言，我们的分析确定了一组在肝癌病理生理学中可能具有临床和生物学意义的代谢物。
The application of non-targeted serum metabolomics profiling represents a noninvasive tool to identify new clinical biomarkers and to provide early diagnostic differentiation, and insight into the pathological mechanisms underlying hepatocellular carcinoma (HCC) progression. In this study, we used proton Nuclear Magnetic Resonance (H-1-NMR) Spectroscopy and multivariate data analysis to profile the serum metabolome of 64 HCC patients, in early (n = 28) and advanced (n = 36) disease stages. We found that H-1-NMR metabolomics profiling could discriminate early from advanced HCC patients with a cross-validated accuracy close to 100%. Orthogonal partial least squares discriminant analysis (OPLS-DA) showed significant changes in serum glucose, lactate, lipids and some amino acids, such as alanine, glutamine, 1-methylhistidine, lysine and valine levels between advanced and early HCC patients. Moreover, in early HCC patients, Kaplan-Meier analysis highlighted the serum tyrosine level as a predictor for overall survival (OS). Overall, our analysis identified a set of metabolites with possible clinical and biological implication in HCC pathophysiology.