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Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets

BACKGROUND: Generally, cancer cells undergo metabolic reprogramming to adapt to energetic and biosynthetic requirements that support their uncontrolled proliferation. However, the mutual relationship between two critical metabolic pathways, glycolysis and oxidative phosphorylation (OXPHOS), remains...

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Autores principales: Bi, Guoshu, Bian, Yunyi, Liang, Jiaqi, Yin, Jiacheng, Li, Runmei, Zhao, Mengnan, Huang, Yiwei, Lu, Tao, Zhan, Cheng, Fan, Hong, Wang, Qun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142489/
https://www.ncbi.nlm.nih.gov/pubmed/34030708
http://dx.doi.org/10.1186/s12967-021-02889-0
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author Bi, Guoshu
Bian, Yunyi
Liang, Jiaqi
Yin, Jiacheng
Li, Runmei
Zhao, Mengnan
Huang, Yiwei
Lu, Tao
Zhan, Cheng
Fan, Hong
Wang, Qun
author_facet Bi, Guoshu
Bian, Yunyi
Liang, Jiaqi
Yin, Jiacheng
Li, Runmei
Zhao, Mengnan
Huang, Yiwei
Lu, Tao
Zhan, Cheng
Fan, Hong
Wang, Qun
author_sort Bi, Guoshu
collection PubMed
description BACKGROUND: Generally, cancer cells undergo metabolic reprogramming to adapt to energetic and biosynthetic requirements that support their uncontrolled proliferation. However, the mutual relationship between two critical metabolic pathways, glycolysis and oxidative phosphorylation (OXPHOS), remains poorly defined. METHODS: We developed a “double-score” system to quantify glycolysis and OXPHOS in 9668 patients across 33 tumor types from The Cancer Genome Atlas and classified them into four metabolic subtypes. Multi-omics bioinformatical analyses was conducted to detect metabolism-related molecular features. RESULTS: Compared with patients with low glycolysis and high OXPHOS (LGHO), those with high glycolysis and low OXPHOS (HGLO) were consistently associated with worse prognosis. We identified common dysregulated molecular features between different metabolic subgroups across multiple cancers, including gene, miRNA, transcription factor, methylation, and somatic alteration, as well as investigated their mutual interfering relationships. CONCLUSION: Overall, this work provides a comprehensive atlas of metabolic heterogeneity on a pan-cancer scale and identified several potential drivers of metabolic rewiring, suggesting corresponding prognostic and therapeutic utility. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-02889-0.
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spelling pubmed-81424892021-05-25 Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets Bi, Guoshu Bian, Yunyi Liang, Jiaqi Yin, Jiacheng Li, Runmei Zhao, Mengnan Huang, Yiwei Lu, Tao Zhan, Cheng Fan, Hong Wang, Qun J Transl Med Research BACKGROUND: Generally, cancer cells undergo metabolic reprogramming to adapt to energetic and biosynthetic requirements that support their uncontrolled proliferation. However, the mutual relationship between two critical metabolic pathways, glycolysis and oxidative phosphorylation (OXPHOS), remains poorly defined. METHODS: We developed a “double-score” system to quantify glycolysis and OXPHOS in 9668 patients across 33 tumor types from The Cancer Genome Atlas and classified them into four metabolic subtypes. Multi-omics bioinformatical analyses was conducted to detect metabolism-related molecular features. RESULTS: Compared with patients with low glycolysis and high OXPHOS (LGHO), those with high glycolysis and low OXPHOS (HGLO) were consistently associated with worse prognosis. We identified common dysregulated molecular features between different metabolic subgroups across multiple cancers, including gene, miRNA, transcription factor, methylation, and somatic alteration, as well as investigated their mutual interfering relationships. CONCLUSION: Overall, this work provides a comprehensive atlas of metabolic heterogeneity on a pan-cancer scale and identified several potential drivers of metabolic rewiring, suggesting corresponding prognostic and therapeutic utility. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-021-02889-0. BioMed Central 2021-05-24 /pmc/articles/PMC8142489/ /pubmed/34030708 http://dx.doi.org/10.1186/s12967-021-02889-0 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
Bi, Guoshu
Bian, Yunyi
Liang, Jiaqi
Yin, Jiacheng
Li, Runmei
Zhao, Mengnan
Huang, Yiwei
Lu, Tao
Zhan, Cheng
Fan, Hong
Wang, Qun
Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets
title Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets
title_full Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets
title_fullStr Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets
title_full_unstemmed Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets
title_short Pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets
title_sort pan-cancer characterization of metabolism-related biomarkers identifies potential therapeutic targets
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142489/
https://www.ncbi.nlm.nih.gov/pubmed/34030708
http://dx.doi.org/10.1186/s12967-021-02889-0
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