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Mitochondrial markers predict survival and progression in non-small cell lung cancer (NSCLC) patients: Use as companion diagnostics

Here, we used an informatics-based approach to identify novel biomarkers of overall survival and tumor progression in non-small cell lung cancer (NSCLC) patients. We determined whether nuclear-encoded genes associated with mitochondrial biogenesis and function can be used to effectively predict clin...

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Autores principales: Sotgia, Federica, Lisanti, Michael P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620239/
https://www.ncbi.nlm.nih.gov/pubmed/28978099
http://dx.doi.org/10.18632/oncotarget.19677
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author Sotgia, Federica
Lisanti, Michael P.
author_facet Sotgia, Federica
Lisanti, Michael P.
author_sort Sotgia, Federica
collection PubMed
description Here, we used an informatics-based approach to identify novel biomarkers of overall survival and tumor progression in non-small cell lung cancer (NSCLC) patients. We determined whether nuclear-encoded genes associated with mitochondrial biogenesis and function can be used to effectively predict clinical outcome in lung cancer. This strategy allowed us to directly provide in silico validation of the prognostic value of these mitochondrial components in large, clinically-relevant, lung cancer patient populations. Towards this end, we used a group of 726 lung cancer patients, with negative surgical margins. Importantly, in this group of cancer patients, markers of cell proliferation (Ki67 and PCNA) were associated with poor overall survival, as would be expected. Similarly, key markers of inflammation (CD163 and CD68) also predicted poor clinical outcome in this patient population. Using this approach, we identified >180 new individual mitochondrial gene probes that effectively predicted significantly reduced overall survival, with hazard-ratios (HR) of up to 4.89 (p<1.0e-16). These nuclear-encoded mitochondrial genes included chaperones, membrane proteins as well as ribosomal proteins (MRPs) and components of the OXPHOS (I-V) complexes. In this analysis, HSPD1, a key marker of mitochondrial biogenesis, had the highest predictive value and was also effective in predicting tumor progression in both smokers and non-smokers alike. In fact, it had even higher predictive value in non-smokers (HR=5.9; p=3.9e-07). Based on this analysis, we conclude that mitochondrial biogenesis should be considered as a new therapeutic target, for the more effective treatment of human lung cancers. The mitochondrial biomarkers that we have identified could serve as new companion diagnostics to assist clinicians in more accurately predicting clinical outcomes in lung cancer patients, driving more personalized cancer therapy.
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spelling pubmed-56202392017-10-03 Mitochondrial markers predict survival and progression in non-small cell lung cancer (NSCLC) patients: Use as companion diagnostics Sotgia, Federica Lisanti, Michael P. Oncotarget Research Paper Here, we used an informatics-based approach to identify novel biomarkers of overall survival and tumor progression in non-small cell lung cancer (NSCLC) patients. We determined whether nuclear-encoded genes associated with mitochondrial biogenesis and function can be used to effectively predict clinical outcome in lung cancer. This strategy allowed us to directly provide in silico validation of the prognostic value of these mitochondrial components in large, clinically-relevant, lung cancer patient populations. Towards this end, we used a group of 726 lung cancer patients, with negative surgical margins. Importantly, in this group of cancer patients, markers of cell proliferation (Ki67 and PCNA) were associated with poor overall survival, as would be expected. Similarly, key markers of inflammation (CD163 and CD68) also predicted poor clinical outcome in this patient population. Using this approach, we identified >180 new individual mitochondrial gene probes that effectively predicted significantly reduced overall survival, with hazard-ratios (HR) of up to 4.89 (p<1.0e-16). These nuclear-encoded mitochondrial genes included chaperones, membrane proteins as well as ribosomal proteins (MRPs) and components of the OXPHOS (I-V) complexes. In this analysis, HSPD1, a key marker of mitochondrial biogenesis, had the highest predictive value and was also effective in predicting tumor progression in both smokers and non-smokers alike. In fact, it had even higher predictive value in non-smokers (HR=5.9; p=3.9e-07). Based on this analysis, we conclude that mitochondrial biogenesis should be considered as a new therapeutic target, for the more effective treatment of human lung cancers. The mitochondrial biomarkers that we have identified could serve as new companion diagnostics to assist clinicians in more accurately predicting clinical outcomes in lung cancer patients, driving more personalized cancer therapy. Impact Journals LLC 2017-07-28 /pmc/articles/PMC5620239/ /pubmed/28978099 http://dx.doi.org/10.18632/oncotarget.19677 Text en Copyright: © 2017 Sotgia and Lisanti http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Sotgia, Federica
Lisanti, Michael P.
Mitochondrial markers predict survival and progression in non-small cell lung cancer (NSCLC) patients: Use as companion diagnostics
title Mitochondrial markers predict survival and progression in non-small cell lung cancer (NSCLC) patients: Use as companion diagnostics
title_full Mitochondrial markers predict survival and progression in non-small cell lung cancer (NSCLC) patients: Use as companion diagnostics
title_fullStr Mitochondrial markers predict survival and progression in non-small cell lung cancer (NSCLC) patients: Use as companion diagnostics
title_full_unstemmed Mitochondrial markers predict survival and progression in non-small cell lung cancer (NSCLC) patients: Use as companion diagnostics
title_short Mitochondrial markers predict survival and progression in non-small cell lung cancer (NSCLC) patients: Use as companion diagnostics
title_sort mitochondrial markers predict survival and progression in non-small cell lung cancer (nsclc) patients: use as companion diagnostics
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620239/
https://www.ncbi.nlm.nih.gov/pubmed/28978099
http://dx.doi.org/10.18632/oncotarget.19677
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