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基于氢核磁共振的血清代谢组学揭示了早期和晚期肝细胞癌阶段不同的特异性生物标志物。

H-NMR Based Serum Metabolomics Highlights Different Specific Biomarkers between Early and Advanced Hepatocellular Carcinoma Stages.

作者信息

Casadei-Gardini Andrea, Del Coco Laura, Marisi Giorgia, Conti Fabio, Rovesti Giulia, Ulivi Paola, Canale Matteo, Frassineti Giovanni Luca, Foschi Francesco Giuseppe, Longo Serena, Fanizzi Francesco Paolo, Giudetti Anna Maria

机构信息

Division of Medical Oncology, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena, 41125 Modena, Italy.

Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy.

出版信息

Cancers (Basel). 2020 Jan 18;12(1):241. doi: 10.3390/cancers12010241.

DOI:10.3390/cancers12010241
PMID:31963766
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7016798/
Abstract

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-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-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.

摘要

非靶向血清代谢组学分析的应用是一种非侵入性工具,可用于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。在本研究中,我们使用质子核磁共振(H-NMR)光谱和多变量数据分析对64例处于疾病早期(n = 28)和晚期(n = 36)的HCC患者的血清代谢组进行分析。我们发现,H-NMR代谢组学分析能够以接近100%的交叉验证准确率区分早期和晚期HCC患者。正交偏最小二乘判别分析(OPLS-DA)显示,晚期和早期HCC患者之间血清葡萄糖、乳酸、脂质以及一些氨基酸(如丙氨酸、谷氨酰胺、1-甲基组氨酸、赖氨酸和缬氨酸)水平存在显著变化。此外,在早期HCC患者中,Kaplan-Meier分析突出了血清酪氨酸水平作为总生存期(OS)的预测指标。总体而言,我们的分析确定了一组在HCC病理生理学中可能具有临床和生物学意义的代谢物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c7/7016798/4c4accc995f4/cancers-12-00241-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c7/7016798/132427b53496/cancers-12-00241-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c7/7016798/6c9bd0b4a153/cancers-12-00241-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c7/7016798/5f0216217cf6/cancers-12-00241-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c7/7016798/4c4accc995f4/cancers-12-00241-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c7/7016798/132427b53496/cancers-12-00241-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c7/7016798/6c9bd0b4a153/cancers-12-00241-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c7/7016798/5f0216217cf6/cancers-12-00241-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75c7/7016798/4c4accc995f4/cancers-12-00241-g004.jpg

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