Cargando…

Altered L-Arginine Metabolic Pathways in Gastric Cancer: Potential Therapeutic Targets and Biomarkers

There is a pressing need for molecular targets and biomarkers in gastric cancer (GC). We aimed at identifying aberrations in L-arginine metabolism with therapeutic and diagnostic potential. Systemic metabolites were quantified using mass spectrometry in 293 individuals and enzymes’ gene expression w...

Descripción completa

Detalles Bibliográficos
Autores principales: Bednarz-Misa, Iwona, Fleszar, Mariusz G., Fortuna, Paulina, Lewandowski, Łukasz, Mierzchała-Pasierb, Magdalena, Diakowska, Dorota, Krzystek-Korpacka, Małgorzata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395015/
https://www.ncbi.nlm.nih.gov/pubmed/34439753
http://dx.doi.org/10.3390/biom11081086
_version_ 1783744076162531328
author Bednarz-Misa, Iwona
Fleszar, Mariusz G.
Fortuna, Paulina
Lewandowski, Łukasz
Mierzchała-Pasierb, Magdalena
Diakowska, Dorota
Krzystek-Korpacka, Małgorzata
author_facet Bednarz-Misa, Iwona
Fleszar, Mariusz G.
Fortuna, Paulina
Lewandowski, Łukasz
Mierzchała-Pasierb, Magdalena
Diakowska, Dorota
Krzystek-Korpacka, Małgorzata
author_sort Bednarz-Misa, Iwona
collection PubMed
description There is a pressing need for molecular targets and biomarkers in gastric cancer (GC). We aimed at identifying aberrations in L-arginine metabolism with therapeutic and diagnostic potential. Systemic metabolites were quantified using mass spectrometry in 293 individuals and enzymes’ gene expression was quantified in 29 paired tumor-normal samples using qPCR and referred to cancer pathology and molecular landscape. Patients with cancer or benign disorders had reduced systemic arginine, citrulline, and ornithine and elevated symmetric dimethylarginine and dimethylamine. Citrulline and ornithine depletion was accentuated in metastasizing cancers. Metabolite diagnostic panel had 91% accuracy in detecting cancer and 70% accuracy in differentiating cancer from benign disorders. Gastric tumors had upregulated NOS2 and downregulated ASL, PRMT2, ORNT1, and DDAH1 expression. NOS2 upregulation was less and ASL downregulation was more pronounced in metastatic cancers. Tumor ASL and PRMT2 expression was inversely related to local advancement. Enzyme up- or downregulation was greater or significant solely in cardia subtype. Metabolic reprogramming in GC includes aberrant L-arginine metabolism, reflecting GC subtype and pathology, and is manifested by altered interplay of its intermediates and enzymes. Exploiting L-arginine metabolic pathways for diagnostic and therapeutic purposes is warranted. Functional studies on ASL, PRMT2, and ORNT1 in GC are needed.
format Online
Article
Text
id pubmed-8395015
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-83950152021-08-28 Altered L-Arginine Metabolic Pathways in Gastric Cancer: Potential Therapeutic Targets and Biomarkers Bednarz-Misa, Iwona Fleszar, Mariusz G. Fortuna, Paulina Lewandowski, Łukasz Mierzchała-Pasierb, Magdalena Diakowska, Dorota Krzystek-Korpacka, Małgorzata Biomolecules Article There is a pressing need for molecular targets and biomarkers in gastric cancer (GC). We aimed at identifying aberrations in L-arginine metabolism with therapeutic and diagnostic potential. Systemic metabolites were quantified using mass spectrometry in 293 individuals and enzymes’ gene expression was quantified in 29 paired tumor-normal samples using qPCR and referred to cancer pathology and molecular landscape. Patients with cancer or benign disorders had reduced systemic arginine, citrulline, and ornithine and elevated symmetric dimethylarginine and dimethylamine. Citrulline and ornithine depletion was accentuated in metastasizing cancers. Metabolite diagnostic panel had 91% accuracy in detecting cancer and 70% accuracy in differentiating cancer from benign disorders. Gastric tumors had upregulated NOS2 and downregulated ASL, PRMT2, ORNT1, and DDAH1 expression. NOS2 upregulation was less and ASL downregulation was more pronounced in metastatic cancers. Tumor ASL and PRMT2 expression was inversely related to local advancement. Enzyme up- or downregulation was greater or significant solely in cardia subtype. Metabolic reprogramming in GC includes aberrant L-arginine metabolism, reflecting GC subtype and pathology, and is manifested by altered interplay of its intermediates and enzymes. Exploiting L-arginine metabolic pathways for diagnostic and therapeutic purposes is warranted. Functional studies on ASL, PRMT2, and ORNT1 in GC are needed. MDPI 2021-07-23 /pmc/articles/PMC8395015/ /pubmed/34439753 http://dx.doi.org/10.3390/biom11081086 Text en © 2021 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
Bednarz-Misa, Iwona
Fleszar, Mariusz G.
Fortuna, Paulina
Lewandowski, Łukasz
Mierzchała-Pasierb, Magdalena
Diakowska, Dorota
Krzystek-Korpacka, Małgorzata
Altered L-Arginine Metabolic Pathways in Gastric Cancer: Potential Therapeutic Targets and Biomarkers
title Altered L-Arginine Metabolic Pathways in Gastric Cancer: Potential Therapeutic Targets and Biomarkers
title_full Altered L-Arginine Metabolic Pathways in Gastric Cancer: Potential Therapeutic Targets and Biomarkers
title_fullStr Altered L-Arginine Metabolic Pathways in Gastric Cancer: Potential Therapeutic Targets and Biomarkers
title_full_unstemmed Altered L-Arginine Metabolic Pathways in Gastric Cancer: Potential Therapeutic Targets and Biomarkers
title_short Altered L-Arginine Metabolic Pathways in Gastric Cancer: Potential Therapeutic Targets and Biomarkers
title_sort altered l-arginine metabolic pathways in gastric cancer: potential therapeutic targets and biomarkers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395015/
https://www.ncbi.nlm.nih.gov/pubmed/34439753
http://dx.doi.org/10.3390/biom11081086
work_keys_str_mv AT bednarzmisaiwona alteredlargininemetabolicpathwaysingastriccancerpotentialtherapeutictargetsandbiomarkers
AT fleszarmariuszg alteredlargininemetabolicpathwaysingastriccancerpotentialtherapeutictargetsandbiomarkers
AT fortunapaulina alteredlargininemetabolicpathwaysingastriccancerpotentialtherapeutictargetsandbiomarkers
AT lewandowskiłukasz alteredlargininemetabolicpathwaysingastriccancerpotentialtherapeutictargetsandbiomarkers
AT mierzchałapasierbmagdalena alteredlargininemetabolicpathwaysingastriccancerpotentialtherapeutictargetsandbiomarkers
AT diakowskadorota alteredlargininemetabolicpathwaysingastriccancerpotentialtherapeutictargetsandbiomarkers
AT krzystekkorpackamałgorzata alteredlargininemetabolicpathwaysingastriccancerpotentialtherapeutictargetsandbiomarkers