Cargando…

Circulating tumor-derived mutant mitochondrial DNA: a predictive biomarker of clinical prognosis in human squamous cell carcinoma

While circulating tumor-derived molecules have been identified in a variety of malignant tumors, it is sometimes difficult to detect the molecular targets due to the lower serum concentration. We report that evaluation of circulating tumor-derived mitochondrial DNA (mtDNA) seems to have novel effici...

Descripción completa

Detalles Bibliográficos
Autores principales: Uzawa, Katsuhiro, Baba, Takao, Uchida, Fumihiko, Yamatoji, Masanobu, Kasamatsu, Atsushi, Sakamoto, Yosuke, Ogawara, Katsunori, Shiiba, Masashi, Bukawa, Hiroki, Tanzawa, Hideki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443250/
https://www.ncbi.nlm.nih.gov/pubmed/22832574
_version_ 1782243535900114944
author Uzawa, Katsuhiro
Baba, Takao
Uchida, Fumihiko
Yamatoji, Masanobu
Kasamatsu, Atsushi
Sakamoto, Yosuke
Ogawara, Katsunori
Shiiba, Masashi
Bukawa, Hiroki
Tanzawa, Hideki
author_facet Uzawa, Katsuhiro
Baba, Takao
Uchida, Fumihiko
Yamatoji, Masanobu
Kasamatsu, Atsushi
Sakamoto, Yosuke
Ogawara, Katsunori
Shiiba, Masashi
Bukawa, Hiroki
Tanzawa, Hideki
author_sort Uzawa, Katsuhiro
collection PubMed
description While circulating tumor-derived molecules have been identified in a variety of malignant tumors, it is sometimes difficult to detect the molecular targets due to the lower serum concentration. We report that evaluation of circulating tumor-derived mitochondrial DNA (mtDNA) seems to have novel efficiency for detecting tumoral micrometastasis. In murine xenografting human oral cancer cells, human mtDNAs could be quantitatively detected from multiple organs and blood samples whereas human nucleic DNAs could not. We also determined if this mtDNA blood test was relevant for patients with oral cancer with no histologic evidence of tumoral cells in their surgical margins. For this, mtDNA from normal and tumorous tissues and serum mtDNA obtained pre and postoperatively was examined at three different regions including the displacement loop, 12S-rRNA, and 16S-rRNA. All recurring patients had significantly higher amounts of mutant mtDNAs in the tumoral tissues compared with the non-recurring group. More importantly, on the blood test with the cut-off point by receiver operating characteristic (ROC) curve analysis, while the vast majority of serum mtDNA samples obtained postoperatively in the recurring cases maintained significantly higher amounts of mutant mtDNAs, the non-recurring cases did not, and they showed good prognosis. This is the first report of this approach for managing patients after resection of oral tumors, and may have substantial diagnostic potential for other tumoral types.
format Online
Article
Text
id pubmed-3443250
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-34432502012-09-27 Circulating tumor-derived mutant mitochondrial DNA: a predictive biomarker of clinical prognosis in human squamous cell carcinoma Uzawa, Katsuhiro Baba, Takao Uchida, Fumihiko Yamatoji, Masanobu Kasamatsu, Atsushi Sakamoto, Yosuke Ogawara, Katsunori Shiiba, Masashi Bukawa, Hiroki Tanzawa, Hideki Oncotarget Brief Reports While circulating tumor-derived molecules have been identified in a variety of malignant tumors, it is sometimes difficult to detect the molecular targets due to the lower serum concentration. We report that evaluation of circulating tumor-derived mitochondrial DNA (mtDNA) seems to have novel efficiency for detecting tumoral micrometastasis. In murine xenografting human oral cancer cells, human mtDNAs could be quantitatively detected from multiple organs and blood samples whereas human nucleic DNAs could not. We also determined if this mtDNA blood test was relevant for patients with oral cancer with no histologic evidence of tumoral cells in their surgical margins. For this, mtDNA from normal and tumorous tissues and serum mtDNA obtained pre and postoperatively was examined at three different regions including the displacement loop, 12S-rRNA, and 16S-rRNA. All recurring patients had significantly higher amounts of mutant mtDNAs in the tumoral tissues compared with the non-recurring group. More importantly, on the blood test with the cut-off point by receiver operating characteristic (ROC) curve analysis, while the vast majority of serum mtDNA samples obtained postoperatively in the recurring cases maintained significantly higher amounts of mutant mtDNAs, the non-recurring cases did not, and they showed good prognosis. This is the first report of this approach for managing patients after resection of oral tumors, and may have substantial diagnostic potential for other tumoral types. Impact Journals LLC 2012-07-25 /pmc/articles/PMC3443250/ /pubmed/22832574 Text en Copyright: © 2012 Uzawa et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
spellingShingle Brief Reports
Uzawa, Katsuhiro
Baba, Takao
Uchida, Fumihiko
Yamatoji, Masanobu
Kasamatsu, Atsushi
Sakamoto, Yosuke
Ogawara, Katsunori
Shiiba, Masashi
Bukawa, Hiroki
Tanzawa, Hideki
Circulating tumor-derived mutant mitochondrial DNA: a predictive biomarker of clinical prognosis in human squamous cell carcinoma
title Circulating tumor-derived mutant mitochondrial DNA: a predictive biomarker of clinical prognosis in human squamous cell carcinoma
title_full Circulating tumor-derived mutant mitochondrial DNA: a predictive biomarker of clinical prognosis in human squamous cell carcinoma
title_fullStr Circulating tumor-derived mutant mitochondrial DNA: a predictive biomarker of clinical prognosis in human squamous cell carcinoma
title_full_unstemmed Circulating tumor-derived mutant mitochondrial DNA: a predictive biomarker of clinical prognosis in human squamous cell carcinoma
title_short Circulating tumor-derived mutant mitochondrial DNA: a predictive biomarker of clinical prognosis in human squamous cell carcinoma
title_sort circulating tumor-derived mutant mitochondrial dna: a predictive biomarker of clinical prognosis in human squamous cell carcinoma
topic Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3443250/
https://www.ncbi.nlm.nih.gov/pubmed/22832574
work_keys_str_mv AT uzawakatsuhiro circulatingtumorderivedmutantmitochondrialdnaapredictivebiomarkerofclinicalprognosisinhumansquamouscellcarcinoma
AT babatakao circulatingtumorderivedmutantmitochondrialdnaapredictivebiomarkerofclinicalprognosisinhumansquamouscellcarcinoma
AT uchidafumihiko circulatingtumorderivedmutantmitochondrialdnaapredictivebiomarkerofclinicalprognosisinhumansquamouscellcarcinoma
AT yamatojimasanobu circulatingtumorderivedmutantmitochondrialdnaapredictivebiomarkerofclinicalprognosisinhumansquamouscellcarcinoma
AT kasamatsuatsushi circulatingtumorderivedmutantmitochondrialdnaapredictivebiomarkerofclinicalprognosisinhumansquamouscellcarcinoma
AT sakamotoyosuke circulatingtumorderivedmutantmitochondrialdnaapredictivebiomarkerofclinicalprognosisinhumansquamouscellcarcinoma
AT ogawarakatsunori circulatingtumorderivedmutantmitochondrialdnaapredictivebiomarkerofclinicalprognosisinhumansquamouscellcarcinoma
AT shiibamasashi circulatingtumorderivedmutantmitochondrialdnaapredictivebiomarkerofclinicalprognosisinhumansquamouscellcarcinoma
AT bukawahiroki circulatingtumorderivedmutantmitochondrialdnaapredictivebiomarkerofclinicalprognosisinhumansquamouscellcarcinoma
AT tanzawahideki circulatingtumorderivedmutantmitochondrialdnaapredictivebiomarkerofclinicalprognosisinhumansquamouscellcarcinoma