Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia

Abstract Epstein Barr virus (EBV) is the etiologic agent involved in numerous human cancers. After infecting the host, EBV establishes a latent infection, with low levels of messenger RNA (mRNA) and protein expression, evolved to evade immune recognition. Conversely, EBV microRNAs (miRNA) are expres...

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Autores principales:	Mercedeh Movassagh, Cliff Oduor, Catherine Forconi, Ann M. Moormann, Jeffrey A. Bailey
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/51b738e0bfe548818e62beacc1811eea
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spelling	oai:doaj.org-article:51b738e0bfe548818e62beacc1811eea2021-12-02T15:12:22ZSensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia10.1038/s41598-019-56472-12045-2322https://doaj.org/article/51b738e0bfe548818e62beacc1811eea2019-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-56472-1https://doaj.org/toc/2045-2322Abstract Epstein Barr virus (EBV) is the etiologic agent involved in numerous human cancers. After infecting the host, EBV establishes a latent infection, with low levels of messenger RNA (mRNA) and protein expression, evolved to evade immune recognition. Conversely, EBV microRNAs (miRNA) are expressed ubiquitously and abundantly within infected cells. Their role in tumor biology and clinical outcomes across the spectrum of cancer is not fully explained. Here, we applied our bioinformatics pipeline for quantitative EBV miRNA detection to examine sequencing data of 8,955 individual tumor samples across 27 tumor types representing the breadth of cancer. We uncover an association of intermediate levels of viral miRNA with decreased survival in adult acute myeloid leukemia (AML) patients (P = 0.00013). Prognostic modeling of this association suggests that increased EBV miRNA levels represent an independent risk factor for poor patient outcomes. Furthermore, we explore differences in expression between elevated and absent viral miRNA loads in adult AML tumors finding that EBV positivity was associated with proinflammatory signals. Together, given no associations were found for pediatric AML, our analyses suggests EBV positivity has the potential for being a prognostic biomarker and might represent a surrogate measure related to immune impairment in adult patients.Mercedeh MovassaghCliff OduorCatherine ForconiAnn M. MoormannJeffrey A. BaileyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-10 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mercedeh Movassagh Cliff Oduor Catherine Forconi Ann M. Moormann Jeffrey A. Bailey Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia
description	Abstract Epstein Barr virus (EBV) is the etiologic agent involved in numerous human cancers. After infecting the host, EBV establishes a latent infection, with low levels of messenger RNA (mRNA) and protein expression, evolved to evade immune recognition. Conversely, EBV microRNAs (miRNA) are expressed ubiquitously and abundantly within infected cells. Their role in tumor biology and clinical outcomes across the spectrum of cancer is not fully explained. Here, we applied our bioinformatics pipeline for quantitative EBV miRNA detection to examine sequencing data of 8,955 individual tumor samples across 27 tumor types representing the breadth of cancer. We uncover an association of intermediate levels of viral miRNA with decreased survival in adult acute myeloid leukemia (AML) patients (P = 0.00013). Prognostic modeling of this association suggests that increased EBV miRNA levels represent an independent risk factor for poor patient outcomes. Furthermore, we explore differences in expression between elevated and absent viral miRNA loads in adult AML tumors finding that EBV positivity was associated with proinflammatory signals. Together, given no associations were found for pediatric AML, our analyses suggests EBV positivity has the potential for being a prognostic biomarker and might represent a surrogate measure related to immune impairment in adult patients.
format	article
author	Mercedeh Movassagh Cliff Oduor Catherine Forconi Ann M. Moormann Jeffrey A. Bailey
author_facet	Mercedeh Movassagh Cliff Oduor Catherine Forconi Ann M. Moormann Jeffrey A. Bailey
author_sort	Mercedeh Movassagh
title	Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia
title_short	Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia
title_full	Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia
title_fullStr	Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia
title_full_unstemmed	Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia
title_sort	sensitive detection of ebv micrornas across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/51b738e0bfe548818e62beacc1811eea
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Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia

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