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Mitochondrial mRNA transcripts predict overall survival, tumor recurrence and progression in serous ovarian cancer: Companion diagnostics for cancer therapy
Here, we performed a systematic analysis to discover new biomarkers of overall survival and tumor progression in ovarian cancer patients. More specifically, we determined whether nuclear-encoded mitochondrial genes related to mitochondrial biogenesis and function are effective in predicting clinical...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620146/ https://www.ncbi.nlm.nih.gov/pubmed/28978006 http://dx.doi.org/10.18632/oncotarget.19963 |
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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 performed a systematic analysis to discover new biomarkers of overall survival and tumor progression in ovarian cancer patients. More specifically, we determined whether nuclear-encoded mitochondrial genes related to mitochondrial biogenesis and function are effective in predicting clinical outcome in ovarian cancer. As a consequence, we are able to provide in silico validation of the prognostic value of these mitochondrial markers, in a well-defined population of ovarian cancer patients. Towards this end, we used a group of N=111 ovarian cancer patients (serous type; stage III), with optimal de-bulking. Importantly, in this group of cancer patients, CA125 and PCNA (conventional markers) were associated with poor overall survival, as would be expected. Using this approach, we identified >100 new individual mitochondrial gene probes that effectively predicted significantly reduced overall survival, with hazard-ratios (HR) of up to 3.68 (p < 9.8e-05). These mitochondrial mRNA transcripts included membrane proteins, chaperones, anti-oxidant enzymes, as well as mitochondrial ribosomal proteins (MRPs) and key members of the OXPHOS (I-V) complexes. Based on this bioinformatics analysis and in silico validation, we conclude that mitochondrial biogenesis and OXPHOS should both be considered as new therapeutic targets, for the more effective treatment of human ovarian cancers. The mitochondrial biomarkers that we have identified could also be employed as new companion diagnostics to assist oncologists in: i) more accurately predicting clinical outcomes and ii) improving the response to therapy, in ovarian cancer patients. |
format | Online Article Text |
id | pubmed-5620146 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56201462017-10-03 Mitochondrial mRNA transcripts predict overall survival, tumor recurrence and progression in serous ovarian cancer: Companion diagnostics for cancer therapy Sotgia, Federica Lisanti, Michael P. Oncotarget Research Paper Here, we performed a systematic analysis to discover new biomarkers of overall survival and tumor progression in ovarian cancer patients. More specifically, we determined whether nuclear-encoded mitochondrial genes related to mitochondrial biogenesis and function are effective in predicting clinical outcome in ovarian cancer. As a consequence, we are able to provide in silico validation of the prognostic value of these mitochondrial markers, in a well-defined population of ovarian cancer patients. Towards this end, we used a group of N=111 ovarian cancer patients (serous type; stage III), with optimal de-bulking. Importantly, in this group of cancer patients, CA125 and PCNA (conventional markers) were associated with poor overall survival, as would be expected. Using this approach, we identified >100 new individual mitochondrial gene probes that effectively predicted significantly reduced overall survival, with hazard-ratios (HR) of up to 3.68 (p < 9.8e-05). These mitochondrial mRNA transcripts included membrane proteins, chaperones, anti-oxidant enzymes, as well as mitochondrial ribosomal proteins (MRPs) and key members of the OXPHOS (I-V) complexes. Based on this bioinformatics analysis and in silico validation, we conclude that mitochondrial biogenesis and OXPHOS should both be considered as new therapeutic targets, for the more effective treatment of human ovarian cancers. The mitochondrial biomarkers that we have identified could also be employed as new companion diagnostics to assist oncologists in: i) more accurately predicting clinical outcomes and ii) improving the response to therapy, in ovarian cancer patients. Impact Journals LLC 2017-08-06 /pmc/articles/PMC5620146/ /pubmed/28978006 http://dx.doi.org/10.18632/oncotarget.19963 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 mRNA transcripts predict overall survival, tumor recurrence and progression in serous ovarian cancer: Companion diagnostics for cancer therapy |
title | Mitochondrial mRNA transcripts predict overall survival, tumor recurrence and progression in serous ovarian cancer: Companion diagnostics for cancer therapy |
title_full | Mitochondrial mRNA transcripts predict overall survival, tumor recurrence and progression in serous ovarian cancer: Companion diagnostics for cancer therapy |
title_fullStr | Mitochondrial mRNA transcripts predict overall survival, tumor recurrence and progression in serous ovarian cancer: Companion diagnostics for cancer therapy |
title_full_unstemmed | Mitochondrial mRNA transcripts predict overall survival, tumor recurrence and progression in serous ovarian cancer: Companion diagnostics for cancer therapy |
title_short | Mitochondrial mRNA transcripts predict overall survival, tumor recurrence and progression in serous ovarian cancer: Companion diagnostics for cancer therapy |
title_sort | mitochondrial mrna transcripts predict overall survival, tumor recurrence and progression in serous ovarian cancer: companion diagnostics for cancer therapy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620146/ https://www.ncbi.nlm.nih.gov/pubmed/28978006 http://dx.doi.org/10.18632/oncotarget.19963 |
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