Cargando…

Navigating through the Lipid Metabolism Maze: Diagnosis and Prognosis Metabolites of Hepatocellular Carcinoma versus Compensated Cirrhosis

(1) Background: The pursuit of finding biomarkers for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has never been so paramount in the days of personalized medicine. The main objective of our study is to identify new biomarkers for diagnosing HCC, and to identify which patients are a...

Descripción completa

Detalles Bibliográficos
Autores principales: Nenu, Iuliana, Stefanescu, Horia, Procopet, Bogdan, Sparchez, Zeno, Minciuna, Iulia, Mocan, Tudor, Leucuta, Daniel, Morar, Corina, Grigorescu, Mircea, Filip, Gabriela Adriana, Socaciu, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910918/
https://www.ncbi.nlm.nih.gov/pubmed/35268381
http://dx.doi.org/10.3390/jcm11051292
_version_ 1784666616757223424
author Nenu, Iuliana
Stefanescu, Horia
Procopet, Bogdan
Sparchez, Zeno
Minciuna, Iulia
Mocan, Tudor
Leucuta, Daniel
Morar, Corina
Grigorescu, Mircea
Filip, Gabriela Adriana
Socaciu, Carmen
author_facet Nenu, Iuliana
Stefanescu, Horia
Procopet, Bogdan
Sparchez, Zeno
Minciuna, Iulia
Mocan, Tudor
Leucuta, Daniel
Morar, Corina
Grigorescu, Mircea
Filip, Gabriela Adriana
Socaciu, Carmen
author_sort Nenu, Iuliana
collection PubMed
description (1) Background: The pursuit of finding biomarkers for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has never been so paramount in the days of personalized medicine. The main objective of our study is to identify new biomarkers for diagnosing HCC, and to identify which patients are at risk of developing tumor recurrence, decompensation, or even possesses the risk of cancer-related death. (2) Methods: We have conducted an untargeted metabolomics study from the serum of 69 European patients—32 compensated cirrhotic patients without HCC (controls), and 37 cirrhotic patients with HCC with compensated underlying liver disease (cases), that underwent curative treatment (surgery or ablation), performing ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-QTOF- (ESI+)-MS) with an emphasis on lipid metabolites. (3) Results: 1,25-dihydroxy cholesterol (m/z = 419.281), myristyl palmitate (m/z = 453.165), 25-hydroxy vitamin D2 (m/z = 413.265), 12-ketodeoxycholic acid (m/z = 391.283), lysoPC (21:4) (m/z = 558.291), and lysoPE (22:2) (m/z = 534.286) represent notable biomarkers that differentiate compensated cirrhosis from early HCC, and ceramide species are depleted in the serum of HCC patients. Regarding prognosis, no metabolite identified in our study could determine tumor relapse. To distinguish between the HCC patients that survived curative treatment and those at risk that developed tumor burden, we have identified two notable phosphocholines (PC (30:2); PC (30:1)) with AUROCs of 0.820 and 0.807, respectively, that seem to increase when patients are at risk. In a univariate analysis, arachidonic acid was the only metabolite to predict decompensation (OR = 0.1, 95% CI: 0–0.16, p < 0.005), while in the multivariate analysis, dismally, no variable was associated with decompensation. Furthermore, in the multivariate analysis, we have found out for the first time that the increased expression of 1,25-dihydroxy cholesterol, myristyl palmitate, 12-keto deoxycholic acid, lysoPC (21:4), and lysoPE (22:2) are independent markers of survival. (4) Conclusions: Our study reveals that lipids play a crucial role in discriminating compensated cirrhosis and early hepatocellular carcinoma, and might represent markers of survival and prognosis in personalized and minimally invasive medicine.
format Online
Article
Text
id pubmed-8910918
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-89109182022-03-11 Navigating through the Lipid Metabolism Maze: Diagnosis and Prognosis Metabolites of Hepatocellular Carcinoma versus Compensated Cirrhosis Nenu, Iuliana Stefanescu, Horia Procopet, Bogdan Sparchez, Zeno Minciuna, Iulia Mocan, Tudor Leucuta, Daniel Morar, Corina Grigorescu, Mircea Filip, Gabriela Adriana Socaciu, Carmen J Clin Med Article (1) Background: The pursuit of finding biomarkers for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has never been so paramount in the days of personalized medicine. The main objective of our study is to identify new biomarkers for diagnosing HCC, and to identify which patients are at risk of developing tumor recurrence, decompensation, or even possesses the risk of cancer-related death. (2) Methods: We have conducted an untargeted metabolomics study from the serum of 69 European patients—32 compensated cirrhotic patients without HCC (controls), and 37 cirrhotic patients with HCC with compensated underlying liver disease (cases), that underwent curative treatment (surgery or ablation), performing ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-QTOF- (ESI+)-MS) with an emphasis on lipid metabolites. (3) Results: 1,25-dihydroxy cholesterol (m/z = 419.281), myristyl palmitate (m/z = 453.165), 25-hydroxy vitamin D2 (m/z = 413.265), 12-ketodeoxycholic acid (m/z = 391.283), lysoPC (21:4) (m/z = 558.291), and lysoPE (22:2) (m/z = 534.286) represent notable biomarkers that differentiate compensated cirrhosis from early HCC, and ceramide species are depleted in the serum of HCC patients. Regarding prognosis, no metabolite identified in our study could determine tumor relapse. To distinguish between the HCC patients that survived curative treatment and those at risk that developed tumor burden, we have identified two notable phosphocholines (PC (30:2); PC (30:1)) with AUROCs of 0.820 and 0.807, respectively, that seem to increase when patients are at risk. In a univariate analysis, arachidonic acid was the only metabolite to predict decompensation (OR = 0.1, 95% CI: 0–0.16, p < 0.005), while in the multivariate analysis, dismally, no variable was associated with decompensation. Furthermore, in the multivariate analysis, we have found out for the first time that the increased expression of 1,25-dihydroxy cholesterol, myristyl palmitate, 12-keto deoxycholic acid, lysoPC (21:4), and lysoPE (22:2) are independent markers of survival. (4) Conclusions: Our study reveals that lipids play a crucial role in discriminating compensated cirrhosis and early hepatocellular carcinoma, and might represent markers of survival and prognosis in personalized and minimally invasive medicine. MDPI 2022-02-26 /pmc/articles/PMC8910918/ /pubmed/35268381 http://dx.doi.org/10.3390/jcm11051292 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nenu, Iuliana
Stefanescu, Horia
Procopet, Bogdan
Sparchez, Zeno
Minciuna, Iulia
Mocan, Tudor
Leucuta, Daniel
Morar, Corina
Grigorescu, Mircea
Filip, Gabriela Adriana
Socaciu, Carmen
Navigating through the Lipid Metabolism Maze: Diagnosis and Prognosis Metabolites of Hepatocellular Carcinoma versus Compensated Cirrhosis
title Navigating through the Lipid Metabolism Maze: Diagnosis and Prognosis Metabolites of Hepatocellular Carcinoma versus Compensated Cirrhosis
title_full Navigating through the Lipid Metabolism Maze: Diagnosis and Prognosis Metabolites of Hepatocellular Carcinoma versus Compensated Cirrhosis
title_fullStr Navigating through the Lipid Metabolism Maze: Diagnosis and Prognosis Metabolites of Hepatocellular Carcinoma versus Compensated Cirrhosis
title_full_unstemmed Navigating through the Lipid Metabolism Maze: Diagnosis and Prognosis Metabolites of Hepatocellular Carcinoma versus Compensated Cirrhosis
title_short Navigating through the Lipid Metabolism Maze: Diagnosis and Prognosis Metabolites of Hepatocellular Carcinoma versus Compensated Cirrhosis
title_sort navigating through the lipid metabolism maze: diagnosis and prognosis metabolites of hepatocellular carcinoma versus compensated cirrhosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910918/
https://www.ncbi.nlm.nih.gov/pubmed/35268381
http://dx.doi.org/10.3390/jcm11051292
work_keys_str_mv AT nenuiuliana navigatingthroughthelipidmetabolismmazediagnosisandprognosismetabolitesofhepatocellularcarcinomaversuscompensatedcirrhosis
AT stefanescuhoria navigatingthroughthelipidmetabolismmazediagnosisandprognosismetabolitesofhepatocellularcarcinomaversuscompensatedcirrhosis
AT procopetbogdan navigatingthroughthelipidmetabolismmazediagnosisandprognosismetabolitesofhepatocellularcarcinomaversuscompensatedcirrhosis
AT sparchezzeno navigatingthroughthelipidmetabolismmazediagnosisandprognosismetabolitesofhepatocellularcarcinomaversuscompensatedcirrhosis
AT minciunaiulia navigatingthroughthelipidmetabolismmazediagnosisandprognosismetabolitesofhepatocellularcarcinomaversuscompensatedcirrhosis
AT mocantudor navigatingthroughthelipidmetabolismmazediagnosisandprognosismetabolitesofhepatocellularcarcinomaversuscompensatedcirrhosis
AT leucutadaniel navigatingthroughthelipidmetabolismmazediagnosisandprognosismetabolitesofhepatocellularcarcinomaversuscompensatedcirrhosis
AT morarcorina navigatingthroughthelipidmetabolismmazediagnosisandprognosismetabolitesofhepatocellularcarcinomaversuscompensatedcirrhosis
AT grigorescumircea navigatingthroughthelipidmetabolismmazediagnosisandprognosismetabolitesofhepatocellularcarcinomaversuscompensatedcirrhosis
AT filipgabrielaadriana navigatingthroughthelipidmetabolismmazediagnosisandprognosismetabolitesofhepatocellularcarcinomaversuscompensatedcirrhosis
AT socaciucarmen navigatingthroughthelipidmetabolismmazediagnosisandprognosismetabolitesofhepatocellularcarcinomaversuscompensatedcirrhosis