Epstein-Barr Virus Promotes Tumorigenicity and Worsens Hodgkin Lymphoma Prognosis by Activating JAK/STAT and NF-κB Signaling Pathways

Q: How was EBV-positive and EBV-negative classical Hodgkin lymphoma compared in this study?

A prospective cohort study evaluated biopsy samples from 64 classical Hodgkin lymphoma patients, dividing them into EBV-positive and EBV-negative groups. mRNA levels and protein end products of JAK/STAT and NF-κB pathway components were measured and compared.

Q: Which pathways and molecules were analyzed for association with prognosis?

The study assessed mRNA expression of JAK2, STAT1, IRF-1, PD-L1, IFN-γ, NF-κB, Bcl-xL, and COX-2, and protein end products of PD-L1, Bcl-xL, and COX-2. Associations were tested against clinicopathological and prognostic parameters.

Q: What outcomes were worse in EBV-positive patients?

EBV-positive classical Hodgkin lymphoma patients showed higher cancer progression and relapse, poorer disease-free survival and overall survival, and higher mortality. They also had more unfavorable clinicopathological parameters such as B-symptoms, extra-nodal involvement, and advanced stage.

Sep 21, 2026

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Epstein-Barr virus (EBV) is present in a substantial fraction of patients with Hodgkin lymphoma, and it can modulate host transcriptional programs during latency. This study evaluated mRNA expression and protein end products of JAK/STAT and NF-κB pathway components and assessed their links with clinicopathological features and prognostic parameters in EBV-positive versus EBV-negative classical Hodgkin lymphoma. Results showed stronger pathway activity in EBV-positive cases, with worse survival and higher relapse rates.

LanguageEnglish

CategoryHealthcare

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Pages13

Reading Time33 min

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What’s Known

Epstein-Barr virus (EBV) activates JAK/STAT and NF-κB pathways in EBV-positive Hodgkin lymphoma

Prognostic role of EBV in classical HL is ambiguous

What’s New

EBV promotes NF-κB and JAK2/STAT1-related proapoptotic/survival protein expression

Targeting NF-κB and JAK2/STAT1 may support treatment of EBV-associated classical Hodgkin lymphoma

Abstract

Background

Methods

Results

Conclusion

Keywords

Introduction

Comparing EBV-positive and-negative classical Hodgkin lymphoma

IJMS Vol 49, No 2, February 2024 Original Article Epstein-Barr Virus Promotes Tumorigenicity and Worsens Hodgkin Lymphoma Prognosis by Activating JAK/STAT and NF-κB Signaling Pathways Mohamed Ali Alabiad1, MD; Warda M. M. Said2 , MD; Rema H Faraj Saad2 , MD; Rawda Balata3 , MD; Asmaa A. Mahmoud4 , MD; Elsayed Anany Metwally5 , MD; Amany Mohamed Shalaby6 , MD; Walaa Samy7, MD; Ahmed M. Yehia8 , MD; Amar Ibrahim Omar Yahia9,10 , MD; Mohammed Alorini11, MD; Doaa I. Abdelrahman1, MD 1Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 2Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi, Libya; 3Department of Clinical Oncology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 4Department of Medical Oncology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 5Hematology Unit, Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 6Depatment of Histology and Cell Biology, Faculty of Medicine, Tanta University, Tanta, Egypt; 7Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 8Department of General Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 9Department of Basic Medical Sciences, College of Medicine, University of Bisha, Bisha, Saudi Arabia; 10Department of Pathology, Faculty of Medicine and Health Sciences, University of Kordofan, Elobeid, Sudan; 11Department of Basic Medical Sciences, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah, Kingdom of Saudi Arabia Correspondence: Mohamed AliAlabiad, MD; Address: Faculty of Medicine, Zagazig University, Postal code: 44519, Zagazig, Egypt Tel: +20 11 50509554 [Email:](Email: maabyad@medicine.zu.edu.eg)[ maabyad@medicine.zu.edu.eg](Email: maabyad@medicine.zu.edu.eg) [Received: 19 November 2022](Received: 19 November 2022) [Revised: 25 April 2023](Revised: 25 April 2023) [Accepted: 30 March 2023](Accepted: 30 March 2023) |
What’s Known
• Epstein-Barr virus (EBV) activates JAK/STAT and NF-κB pathways in patients with EBV-positive Hodgkin lymphoma (HL) .
• The role of EBV in the prognosis of classical HL remains ambiguous and controversial.

What’s New | | --- | | • EBV promotes the expression of proapoptotic and survival immortalization proteins of NF-κB and JAK2/STAT1 pathways. EBV-positive is associated with poor clinicopathological and survival outcomes in HL patients.
• Therapeutic targeting of NF-κB and JAK2/STAT1 pathways could potentially contribute to the treatment of patients with EBV-associated CHL. | Abstract Background: Epstein-Barr virus (EBV) is detected in 40% of patients with Hodgkin lymphoma (HL). During latency, EBV induces epigenetic alterations to the host genome and decreases the expression of pro-apoptotic proteins. The present study aimed to evaluate the expression levels of mRNA molecules and the end product of proteins for the JAK/STAT and NF-κB pathways, and their association with clinicopathological and prognostic parameters in patients with EBV-positive and-negative classical Hodgkin lymphoma (CHL). Methods: A prospective cohort study was conducted from 2017 to 2022 at the Faculty of Medicine, Zagazig University Hospital (Zagazig, Egypt). Biopsy samples of 64 patients with CHL were divided into EBV-positive and EBV-negative groups. The expression levels of mRNA molecules (JAK2, STAT1, IRF-1, PD-L1, IFN-γ, NF-κB, Bcl-xL, COX-2) and the end product of proteins (PD-L1, Bcl-xL, COX-2) were determined and compared with clinicopathological and prognostic parameters. Data were analyzed using the Chi square test and Kaplan-Meier estimate. Results: EBV-positive CHL patients were significantly associated with positive expression of mRNAs molecules (P<0.001) and the end product of proteins (P<0.001) for the JAK/STAT and NF-κB pathways, B-symptoms (P=0.022), extra-nodal involvement (P=0.017)

FAQs

How was EBV-positive and EBV-negative classical Hodgkin lymphoma compared in this study?

A prospective cohort study evaluated biopsy samples from 64 classical Hodgkin lymphoma patients, dividing them into EBV-positive and EBV-negative groups. mRNA levels and protein end products of JAK/STAT and NF-κB pathway components were measured and compared.

Which pathways and molecules were analyzed for association with prognosis?

The study assessed mRNA expression of JAK2, STAT1, IRF-1, PD-L1, IFN-γ, NF-κB, Bcl-xL, and COX-2, and protein end products of PD-L1, Bcl-xL, and COX-2. Associations were tested against clinicopathological and prognostic parameters.

What outcomes were worse in EBV-positive patients?

EBV-positive classical Hodgkin lymphoma patients showed higher cancer progression and relapse, poorer disease-free survival and overall survival, and higher mortality. They also had more unfavorable clinicopathological parameters such as B-symptoms, extra-nodal involvement, and advanced stage.

Sep 21, 2026

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