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Cancer Metabolic Subtypes and Their Association with Molecular and Clinical Features

SIMPLE SUMMARY: The metabolic alterations characteristic of cancer cells play a significant role in tumors’ natural history and response to therapy. Recent technological advances have allowed the production of unprecedented amounts of data on many types of cancers. We exploited the most comprehensiv...

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Autores principales: Moiso, Enrico, Provero, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104370/
https://www.ncbi.nlm.nih.gov/pubmed/35565274
http://dx.doi.org/10.3390/cancers14092145
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author Moiso, Enrico
Provero, Paolo
author_facet Moiso, Enrico
Provero, Paolo
author_sort Moiso, Enrico
collection PubMed
description SIMPLE SUMMARY: The metabolic alterations characteristic of cancer cells play a significant role in tumors’ natural history and response to therapy. Recent technological advances have allowed the production of unprecedented amounts of data on many types of cancers. We exploited the most comprehensive collection of such data, The Cancer Genome Atlas (TCGA), to systematically investigate the associations between metabolic alterations and other tumor features. We used sets of genes known to be associated with specific metabolic pathways to classify patients into “metabolic subtypes”. Then, we systematically looked for associations between the metabolic subtypes and other tumor features, including histological classification, patient survival, and genome alterations. Our results, while correlative in nature, can provide a guide to the formulation of specific mechanistic hypotheses to be tested experimentally so as to improve our understanding of the biology of cancer and our ability to tailor therapeutic interventions to the specific features of each patient. ABSTRACT: The alterations of metabolic pathways in cancer have been investigated for many years, beginning long before the discovery of the role of oncogenes and tumor suppressors, and the last few years have witnessed renewed interest in this topic. Large-scale molecular and clinical data on tens of thousands of samples allow us to tackle the problem from a general point of view. Here, we show that transcriptomic profiles of tumors can be exploited to define metabolic cancer subtypes, which can be systematically investigated for associations with other molecular and clinical data. We find thousands of significant associations between metabolic subtypes and molecular features such as somatic mutations, structural variants, epigenetic modifications, protein abundance and activation, and with clinical/phenotypic data, including survival probability, tumor grade, and histological types, which we make available to the community in a dedicated web resource. Our work provides a methodological framework and a rich database of statistical associations, which will contribute to the understanding of the role of metabolic alterations in cancer and to the development of precision therapeutic strategies.
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spelling pubmed-91043702022-05-14 Cancer Metabolic Subtypes and Their Association with Molecular and Clinical Features Moiso, Enrico Provero, Paolo Cancers (Basel) Article SIMPLE SUMMARY: The metabolic alterations characteristic of cancer cells play a significant role in tumors’ natural history and response to therapy. Recent technological advances have allowed the production of unprecedented amounts of data on many types of cancers. We exploited the most comprehensive collection of such data, The Cancer Genome Atlas (TCGA), to systematically investigate the associations between metabolic alterations and other tumor features. We used sets of genes known to be associated with specific metabolic pathways to classify patients into “metabolic subtypes”. Then, we systematically looked for associations between the metabolic subtypes and other tumor features, including histological classification, patient survival, and genome alterations. Our results, while correlative in nature, can provide a guide to the formulation of specific mechanistic hypotheses to be tested experimentally so as to improve our understanding of the biology of cancer and our ability to tailor therapeutic interventions to the specific features of each patient. ABSTRACT: The alterations of metabolic pathways in cancer have been investigated for many years, beginning long before the discovery of the role of oncogenes and tumor suppressors, and the last few years have witnessed renewed interest in this topic. Large-scale molecular and clinical data on tens of thousands of samples allow us to tackle the problem from a general point of view. Here, we show that transcriptomic profiles of tumors can be exploited to define metabolic cancer subtypes, which can be systematically investigated for associations with other molecular and clinical data. We find thousands of significant associations between metabolic subtypes and molecular features such as somatic mutations, structural variants, epigenetic modifications, protein abundance and activation, and with clinical/phenotypic data, including survival probability, tumor grade, and histological types, which we make available to the community in a dedicated web resource. Our work provides a methodological framework and a rich database of statistical associations, which will contribute to the understanding of the role of metabolic alterations in cancer and to the development of precision therapeutic strategies. MDPI 2022-04-25 /pmc/articles/PMC9104370/ /pubmed/35565274 http://dx.doi.org/10.3390/cancers14092145 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
Moiso, Enrico
Provero, Paolo
Cancer Metabolic Subtypes and Their Association with Molecular and Clinical Features
title Cancer Metabolic Subtypes and Their Association with Molecular and Clinical Features
title_full Cancer Metabolic Subtypes and Their Association with Molecular and Clinical Features
title_fullStr Cancer Metabolic Subtypes and Their Association with Molecular and Clinical Features
title_full_unstemmed Cancer Metabolic Subtypes and Their Association with Molecular and Clinical Features
title_short Cancer Metabolic Subtypes and Their Association with Molecular and Clinical Features
title_sort cancer metabolic subtypes and their association with molecular and clinical features
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104370/
https://www.ncbi.nlm.nih.gov/pubmed/35565274
http://dx.doi.org/10.3390/cancers14092145
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