Extracellular vesicle-associated repetitive element DNAs as candidate osteosarcoma biomarkers

Abstract Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults. Despite that high-risk factors have been identified, no test for early detection is available. This study aimed to identify circulating nucleic acid sequences associated with serum extracellular vesicle...

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Autores principales:	Linda Cambier, Kevin Stachelek, Martin Triska, Rima Jubran, Manyu Huang, Wuyin Li, Jianying Zhang, Jitian Li, David Cobrinik
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ccd14187fd9141e988c7227eec6aca8a
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spelling	oai:doaj.org-article:ccd14187fd9141e988c7227eec6aca8a2021-12-02T15:08:23ZExtracellular vesicle-associated repetitive element DNAs as candidate osteosarcoma biomarkers10.1038/s41598-020-77398-z2045-2322https://doaj.org/article/ccd14187fd9141e988c7227eec6aca8a2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-77398-zhttps://doaj.org/toc/2045-2322Abstract Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults. Despite that high-risk factors have been identified, no test for early detection is available. This study aimed to identify circulating nucleic acid sequences associated with serum extracellular vesicle (EV) preparations at the time of OS diagnosis, as a step towards an OS early detection assay. Sequencing of small nucleic acids extracted from serum EV preparations revealed increased representation of diverse repetitive element sequences in OS patient versus control sera. Analysis of a validation cohort using qPCR of PEG-precipitated EV preparations revealed the over-representation of HSATI, HSATII, LINE1-P1, and Charlie 3 at the DNA but not RNA level, with receiver operating characteristic (ROC) area under the curve (AUC) ≥ 0.90. HSATI and HSATII DNAs co-purified with EVs prepared by precipitation and size exclusion chromatography but not by exosome immunocapture, indicative of packaging in a non-exosomal complex. The consistent over-representation of EV-associated repetitive element DNA sequences suggests their potential utility as biomarkers for OS and perhaps other cancers.Linda CambierKevin StachelekMartin TriskaRima JubranManyu HuangWuyin LiJianying ZhangJitian LiDavid CobrinikNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Linda Cambier Kevin Stachelek Martin Triska Rima Jubran Manyu Huang Wuyin Li Jianying Zhang Jitian Li David Cobrinik Extracellular vesicle-associated repetitive element DNAs as candidate osteosarcoma biomarkers
description	Abstract Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults. Despite that high-risk factors have been identified, no test for early detection is available. This study aimed to identify circulating nucleic acid sequences associated with serum extracellular vesicle (EV) preparations at the time of OS diagnosis, as a step towards an OS early detection assay. Sequencing of small nucleic acids extracted from serum EV preparations revealed increased representation of diverse repetitive element sequences in OS patient versus control sera. Analysis of a validation cohort using qPCR of PEG-precipitated EV preparations revealed the over-representation of HSATI, HSATII, LINE1-P1, and Charlie 3 at the DNA but not RNA level, with receiver operating characteristic (ROC) area under the curve (AUC) ≥ 0.90. HSATI and HSATII DNAs co-purified with EVs prepared by precipitation and size exclusion chromatography but not by exosome immunocapture, indicative of packaging in a non-exosomal complex. The consistent over-representation of EV-associated repetitive element DNA sequences suggests their potential utility as biomarkers for OS and perhaps other cancers.
format	article
author	Linda Cambier Kevin Stachelek Martin Triska Rima Jubran Manyu Huang Wuyin Li Jianying Zhang Jitian Li David Cobrinik
author_facet	Linda Cambier Kevin Stachelek Martin Triska Rima Jubran Manyu Huang Wuyin Li Jianying Zhang Jitian Li David Cobrinik
author_sort	Linda Cambier
title	Extracellular vesicle-associated repetitive element DNAs as candidate osteosarcoma biomarkers
title_short	Extracellular vesicle-associated repetitive element DNAs as candidate osteosarcoma biomarkers
title_full	Extracellular vesicle-associated repetitive element DNAs as candidate osteosarcoma biomarkers
title_fullStr	Extracellular vesicle-associated repetitive element DNAs as candidate osteosarcoma biomarkers
title_full_unstemmed	Extracellular vesicle-associated repetitive element DNAs as candidate osteosarcoma biomarkers
title_sort	extracellular vesicle-associated repetitive element dnas as candidate osteosarcoma biomarkers
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ccd14187fd9141e988c7227eec6aca8a
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Extracellular vesicle-associated repetitive element DNAs as candidate osteosarcoma biomarkers

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