Sensitive detection of EBV microRNAs across cancer spectrum reveals association with decreased survival in adult acute myelocytic leukemia
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Publication Date
2019Author
Mercedeh Movassagh1, Clif Oduor2,3, Catherine Forconi 4, Ann M. Moormann4 & JefreyA. Bailey
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Show full item recordAbstract/ Overview
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 diferences
in expression between elevated and absent viral miRNA loads in adult AML tumors fnding that EBV
positivity was associated with proinfammatory 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.