Metabolomics-Guided Identification of a Distinctive Hepatocellular Carcinoma Signature
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 manifes...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/12/3232 |
| _version_ | 1797436100738809856 |
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| author | Vincent Tambay Valérie-Ann Raymond Corentine Goossens Louise Rousseau Simon Turcotte Marc Bilodeau |
| author_facet | Vincent Tambay Valérie-Ann Raymond Corentine Goossens Louise Rousseau Simon Turcotte Marc Bilodeau |
| author_sort | Vincent Tambay |
| collection | DOAJ |
| description | 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 <sup>1</sup>H Nuclear Magnetic Resonance (<sup>1</sup>H-NMR) spectroscopy whereas specific metabolites were quantified using targeted liquid chromatography–mass spectrometry (LC/MS). Results: Principal component analysis (PCA) within our <sup>1</sup>H-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, <sup>1</sup>H-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. |
| first_indexed | 2024-03-09T10:57:48Z |
| format | Article |
| id | doaj.art-fd8432c4909d4817b55a4a74202a53ab |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T10:57:48Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-fd8432c4909d4817b55a4a74202a53ab2023-12-01T01:33:13ZengMDPI AGCancers2072-66942023-06-011512323210.3390/cancers15123232Metabolomics-Guided Identification of a Distinctive Hepatocellular Carcinoma SignatureVincent Tambay0Valérie-Ann Raymond1Corentine Goossens2Louise Rousseau3Simon Turcotte4Marc Bilodeau5Laboratoire d’Hépatologie Cellulaire, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, QC H2X0A9, CanadaLaboratoire d’Hépatologie Cellulaire, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, QC H2X0A9, CanadaLaboratoire d’Hépatologie Cellulaire, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, QC H2X0A9, CanadaBiobanque et Base de Données Hépatobiliaire et Pancréatique, Centre Hospitalier de l’Université de Montréal, Montréal, QC H2X0C1, CanadaBiobanque et Base de Données Hépatobiliaire et Pancréatique, Centre Hospitalier de l’Université de Montréal, Montréal, QC H2X0C1, CanadaLaboratoire d’Hépatologie Cellulaire, Centre de Recherche du Centre Hospitalier de l’Université de Montréal, Montréal, QC H2X0A9, CanadaBackground: 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 <sup>1</sup>H Nuclear Magnetic Resonance (<sup>1</sup>H-NMR) spectroscopy whereas specific metabolites were quantified using targeted liquid chromatography–mass spectrometry (LC/MS). Results: Principal component analysis (PCA) within our <sup>1</sup>H-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, <sup>1</sup>H-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.https://www.mdpi.com/2072-6694/15/12/3232liverhepatocellular carcinomametabolic reprogrammingmetabolomicsliquid chromatography–mass spectrometryNMR spectroscopy |
| spellingShingle | Vincent Tambay Valérie-Ann Raymond Corentine Goossens Louise Rousseau Simon Turcotte Marc Bilodeau Metabolomics-Guided Identification of a Distinctive Hepatocellular Carcinoma Signature Cancers liver hepatocellular carcinoma metabolic reprogramming metabolomics liquid chromatography–mass spectrometry NMR spectroscopy |
| title | Metabolomics-Guided Identification of a Distinctive Hepatocellular Carcinoma Signature |
| title_full | Metabolomics-Guided Identification of a Distinctive Hepatocellular Carcinoma Signature |
| title_fullStr | Metabolomics-Guided Identification of a Distinctive Hepatocellular Carcinoma Signature |
| title_full_unstemmed | Metabolomics-Guided Identification of a Distinctive Hepatocellular Carcinoma Signature |
| title_short | Metabolomics-Guided Identification of a Distinctive Hepatocellular Carcinoma Signature |
| title_sort | metabolomics guided identification of a distinctive hepatocellular carcinoma signature |
| topic | liver hepatocellular carcinoma metabolic reprogramming metabolomics liquid chromatography–mass spectrometry NMR spectroscopy |
| url | https://www.mdpi.com/2072-6694/15/12/3232 |
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