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Inflammatory metabolic profile of South African patients with prostate cancer

BACKGROUND: Men with African ancestry are more likely to develop aggressive prostate cancer (PCa) and to die from this disease. The study of PCa in the South African population represents an opportunity for biomedical research due to the high prevalence of aggressive PCa. While inflammation is known...

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Autores principales: Cacciatore, Stefano, Wium, Martha, Licari, Cristina, Ajayi-Smith, Aderonke, Masieri, Lorenzo, Anderson, Chanelle, Salukazana, Azola Samkele, Kaestner, Lisa, Carini, Marco, Carbone, Giuseppina M., Catapano, Carlo V., Loda, Massimo, Libermann, Towia A., Zerbini, Luiz F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336341/
https://www.ncbi.nlm.nih.gov/pubmed/34344464
http://dx.doi.org/10.1186/s40170-021-00265-6
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author Cacciatore, Stefano
Wium, Martha
Licari, Cristina
Ajayi-Smith, Aderonke
Masieri, Lorenzo
Anderson, Chanelle
Salukazana, Azola Samkele
Kaestner, Lisa
Carini, Marco
Carbone, Giuseppina M.
Catapano, Carlo V.
Loda, Massimo
Libermann, Towia A.
Zerbini, Luiz F.
author_facet Cacciatore, Stefano
Wium, Martha
Licari, Cristina
Ajayi-Smith, Aderonke
Masieri, Lorenzo
Anderson, Chanelle
Salukazana, Azola Samkele
Kaestner, Lisa
Carini, Marco
Carbone, Giuseppina M.
Catapano, Carlo V.
Loda, Massimo
Libermann, Towia A.
Zerbini, Luiz F.
author_sort Cacciatore, Stefano
collection PubMed
description BACKGROUND: Men with African ancestry are more likely to develop aggressive prostate cancer (PCa) and to die from this disease. The study of PCa in the South African population represents an opportunity for biomedical research due to the high prevalence of aggressive PCa. While inflammation is known to play a significant role in PCa progression, its association with tumor stage in populations of African descent has not been explored in detail. Identification of new metabolic biomarkers of inflammation may improve diagnosis of patients with aggressive PCa. METHODS: Plasma samples were profiled from 41 South African men with PCa using nuclear magnetic resonance (NMR) spectroscopy. A total of 41 features, including metabolites, lipid classes, total protein, and the inflammatory NMR markers, GlycA, and GlycB, were quantified from each NMR spectrum. The Bruker’s B.I.-LISA protocols were used to characterize 114 parameters related to the lipoproteins. The unsupervised KODAMA method was used to stratify the patients of our cohort based on their metabolic profile. RESULTS: We found that the plasma of patients with very high risk, aggressive PCa and high level of C-reactive protein have a peculiar metabolic phenotype (metabotype) characterized by extremely high levels of GlycA and GlycB. The inflammatory processes linked to the higher level of GlycA and GlycB are characterized by a deep change of the plasma metabolome that may be used to improve the stratification of patients with PCa. We also identified a not previously known relationship between high values of VLDL and low level of GlycB in a different metabotype of patients characterized by lower-risk PCa. CONCLUSIONS: For the first time, a portrait of the metabolic changes in African men with PCa has been delineated indicating a strong association between inflammation and metabolic profiles. Our findings indicate how the metabolic profile could be used to identify those patients with high level of inflammation, characterized by aggressive PCa and short life expectancy. Integrating a metabolomic analysis as a tool for patient stratification could be important for opening the door to the development of new therapies. Further investigations are needed to understand the prevalence of an inflammatory metabotype in patients with aggressive PCa. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40170-021-00265-6.
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spelling pubmed-83363412021-08-04 Inflammatory metabolic profile of South African patients with prostate cancer Cacciatore, Stefano Wium, Martha Licari, Cristina Ajayi-Smith, Aderonke Masieri, Lorenzo Anderson, Chanelle Salukazana, Azola Samkele Kaestner, Lisa Carini, Marco Carbone, Giuseppina M. Catapano, Carlo V. Loda, Massimo Libermann, Towia A. Zerbini, Luiz F. Cancer Metab Research BACKGROUND: Men with African ancestry are more likely to develop aggressive prostate cancer (PCa) and to die from this disease. The study of PCa in the South African population represents an opportunity for biomedical research due to the high prevalence of aggressive PCa. While inflammation is known to play a significant role in PCa progression, its association with tumor stage in populations of African descent has not been explored in detail. Identification of new metabolic biomarkers of inflammation may improve diagnosis of patients with aggressive PCa. METHODS: Plasma samples were profiled from 41 South African men with PCa using nuclear magnetic resonance (NMR) spectroscopy. A total of 41 features, including metabolites, lipid classes, total protein, and the inflammatory NMR markers, GlycA, and GlycB, were quantified from each NMR spectrum. The Bruker’s B.I.-LISA protocols were used to characterize 114 parameters related to the lipoproteins. The unsupervised KODAMA method was used to stratify the patients of our cohort based on their metabolic profile. RESULTS: We found that the plasma of patients with very high risk, aggressive PCa and high level of C-reactive protein have a peculiar metabolic phenotype (metabotype) characterized by extremely high levels of GlycA and GlycB. The inflammatory processes linked to the higher level of GlycA and GlycB are characterized by a deep change of the plasma metabolome that may be used to improve the stratification of patients with PCa. We also identified a not previously known relationship between high values of VLDL and low level of GlycB in a different metabotype of patients characterized by lower-risk PCa. CONCLUSIONS: For the first time, a portrait of the metabolic changes in African men with PCa has been delineated indicating a strong association between inflammation and metabolic profiles. Our findings indicate how the metabolic profile could be used to identify those patients with high level of inflammation, characterized by aggressive PCa and short life expectancy. Integrating a metabolomic analysis as a tool for patient stratification could be important for opening the door to the development of new therapies. Further investigations are needed to understand the prevalence of an inflammatory metabotype in patients with aggressive PCa. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40170-021-00265-6. BioMed Central 2021-08-03 /pmc/articles/PMC8336341/ /pubmed/34344464 http://dx.doi.org/10.1186/s40170-021-00265-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Cacciatore, Stefano
Wium, Martha
Licari, Cristina
Ajayi-Smith, Aderonke
Masieri, Lorenzo
Anderson, Chanelle
Salukazana, Azola Samkele
Kaestner, Lisa
Carini, Marco
Carbone, Giuseppina M.
Catapano, Carlo V.
Loda, Massimo
Libermann, Towia A.
Zerbini, Luiz F.
Inflammatory metabolic profile of South African patients with prostate cancer
title Inflammatory metabolic profile of South African patients with prostate cancer
title_full Inflammatory metabolic profile of South African patients with prostate cancer
title_fullStr Inflammatory metabolic profile of South African patients with prostate cancer
title_full_unstemmed Inflammatory metabolic profile of South African patients with prostate cancer
title_short Inflammatory metabolic profile of South African patients with prostate cancer
title_sort inflammatory metabolic profile of south african patients with prostate cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336341/
https://www.ncbi.nlm.nih.gov/pubmed/34344464
http://dx.doi.org/10.1186/s40170-021-00265-6
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