Metabolomics-Guided Identification of a Distinctive Hepatocellular Carcinoma Signature

Author:

Tambay Vincent1ORCID,Raymond Valérie-Ann1,Goossens Corentine1,Rousseau Louise2,Turcotte Simon23,Bilodeau Marc14ORCID

Affiliation:

1. Laboratoire d’Hépatologie Cellulaire, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, QC H2X0A9, Canada

2. Biobanque et Base de Données Hépatobiliaire et Pancréatique, Centre Hospitalier de l’Université de Montréal, Montréal, QC H2X0C1, Canada

3. Département de Chirurgie, Service de Transplantation Hépatique et de Chirurgie Hépatobiliaire et Pancréatique, Centre Hospitalier de l’Université de Montréal, Montréal, QC H2X0C1, Canada

4. Département de Médecine, Université de Montréal, Montréal, QC H3T1J4, Canada

Abstract

Background: Hepatocellular carcinoma (HCC) is a major contributor to cancer-related morbidity and mortality burdens globally. Given the fundamental metabolic activity of hepatocytes within the liver, hepatocarcinogenesis is bound to be characterized by alterations in metabolite profiles as a manifestation of metabolic reprogramming. Methods: HCC and adjacent non-tumoral liver specimens were obtained from patients after HCC resection. Global patterns in tissue metabolites were identified using non-targeted 1H Nuclear Magnetic Resonance (1H-NMR) spectroscopy whereas specific metabolites were quantified using targeted liquid chromatography–mass spectrometry (LC/MS). Results: Principal component analysis (PCA) within our 1H-NMR dataset identified a principal component (PC) one of 53.3%, along which the two sample groups were distinctively clustered. Univariate analysis of tissue specimens identified more than 150 metabolites significantly altered in HCC compared to non-tumoral liver. For LC/MS, PCA identified a PC1 of 45.2%, along which samples from HCC tissues and non-tumoral tissues were clearly separated. Supervised analysis (PLS–DA) identified decreases in tissue glutathione, succinate, glycerol-3-phosphate, alanine, malate, and AMP as the most important contributors to the metabolomic signature of HCC by LC/MS. Conclusions: Together, 1H-NMR and LC/MS metabolomics have the capacity to distinguish HCC from non-tumoral liver. The characterization of such distinct profiles of metabolite abundances underscores the major metabolic alterations that result from hepatocarcinogenesis.

Funder

Chaire de recherche en hépatologie Novartis—Fondation canadienne du foie de l’Université de Montréal

Chaire Roger Des Groseillers d’oncologie chirurgicale hépatobiliaire et pancréatique de l’Université de Montréal

FRQS Young Clinician Scientist Seed

FRQS Clinician Scientist Junior-one and two Salary

Institut du Cancer de Montréal establishment award

Canadian Foundation for Innovation Award

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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