Expressionsmuster von EBV mikroRNAs in Hodgkin Lymphomen

by Laura Vorwerk-Redenbach née Redenbach
Doctoral thesis
Date of Examination:2023-03-29
Date of issue:2023-03-24
Advisor:Prof. Dr. Christine Stadelmann-Nessler
Referee:Prof. Dr. Christine Stadelmann-Nessler
Referee:Prof. Dr. Dieter Kube
Referee:Prof. Dr. Matthias Dobbelstein
Persistent Address: http://dx.doi.org/10.53846/goediss-9809

 

 

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Abstract

English

Epstein-Barr virus encodes 40 different miRNAs with considerable impact on cellular functions of the latently infected cell. In this study EBV miRNA expression patterns in EBV-positive Hodgkin lymphoma and other malignant B cell proliferative disorders were established. With an extensive qPCR study on archival tissue it was found an expression of EBV BART miRNAs in EBV-positive Hodgkin lymphoma that resembles an EBV latency type II expression pattern. At the moment several methods such as immunohistochemistry for EBV proteins or in situ hybridization for EBER1 are used for EBV detection in clinical samples. EBV-miRNA qPCR is feasible with tissue specimens even with highly degraded RNA due to the greater stability of miRNAs. EBV status of Hodgkin lymphoma correlates well with EBV miRNA expression. This method provides an additional diagnostic tool for EBV detection in archival tissue with a sensitivity and specificity comparable to in situ hybridization. Statistical analyses were performed with GraphPad Prism and Excel. Receiver operator characteristic curves (ROC) were computed and the area under the curve (AUC) was calculated to assess the discriminatory power of individual miRNA qPCR reactions. Using a computer prediction, the overexpressed EBV mRNAs with potential human target mRNA transcripts were matched, which showed an accumulation of miRNA binding sites in transcription regulating factors. It was shown that EBV miRNAs have influence on factors such as viral latency or immune escape of the virus and may have a potential relevance in the pathogenesis of lymphomas and other malignancies.
Keywords: EBV; hodgkin lymphoma; mirna
 
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