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 (1H-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 1H-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.
Highlights
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide.The disease displays a complex molecular landscape that hampers patient’s prognosis and therapy [1].hepatocellular carcinoma (HCC) commonly arises in people with underlying liver diseases associated to viral infections, toxic, metabolic and immune factors [1]. many therapeutic approaches have so far been established for HCC treatment, the unavailability of adequate biomarkers for early HCC diagnosis causes a poor prognosis
The 36 ADV HCC patients were treated with sorafenib, and recruited in the study between March 2016 and June 2018, with a median overall survival (OS) of 13.1 months
We found that 1 H-Nuclear Magnetic Resonance (1 H-Nuclear Magnetic Resonance (NMR)) metabolomics profiling could discriminate early from advanced HCC patients
Summary
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide.The disease displays a complex molecular landscape that hampers patient’s prognosis and therapy [1].HCC commonly arises in people with underlying liver diseases associated to viral infections (chronic hepatitis B and C), toxic (alcohol and aflatoxin), metabolic (diabetes, hemochromatosis, Cancers 2020, 12, 241; doi:10.3390/cancers12010241 www.mdpi.com/journal/cancersCancers 2020, 12, 241 and non-alcoholic fatty liver disease) and immune (autoimmune hepatitis and primary biliary) factors [1]. many therapeutic approaches have so far been established for HCC treatment, the unavailability of adequate biomarkers for early HCC diagnosis causes a poor prognosis. In the last few years, metabolite quantification by Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy approaches have been used to obtain a global, unbiased view of small molecules in biofluids and organs, contributing to the understanding of the molecular characteristics of many diseases. These approaches were used to define a series of biomarkers for early diagnoses and treatments of different diseases [6,7,8,9]
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