Document Type : Original Article(s)

Authors

• Mohamed Ali Alabiad ¹
• Warda M. M. Said ²
• Rema H Faraj Saad ²
• Rawda Balata ³
• Asmaa A. Mahmoud ⁴
• Elsayed Anany Metwally ⁵
• Amany Mohamed Shalaby ⁵
• Walaa Samy ⁶
• Ahmed M. Yehia ⁷
• Amar Ibrahim Omar Yahia ^{8, 9}
• Mohammed Alorini ¹⁰
• Doaa I. Abdelrahman ¹¹

¹ Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

² Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi, Libya

³ Department of Clinical Oncology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

⁴ Department of Medical Oncology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

⁵ Hematology Unit, Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt

⁶ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

⁷ Department of General Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt

⁸ Department of Basic Medical Sciences, College of Medicine, University of Bisha, Bisha, Saudi Arabia

⁹ Department of Pathology, Faculty of Medicine and Health Sciences, University of Kordofan, Elobeid, Sudan

¹⁰ Department of Basic Medical Sciences, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah, Kingdom of Saudi Arabia

¹¹ Department of Pathology, Faculty of Medicine, Zagazig University, Egypt.Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

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), and advanced stage of CHL (P=0.018). These patients were more susceptible to cancer progression, higher incidence of relapse (P=0.008), poor disease-free survival rate (P=0.013), poor overall survival rate (P=0.028), and higher mortality rate (P=0.015).
Conclusion: Through the activation of JAK/STAT and NF-κB signaling pathways, EBV-positive CHL is associated with poor clinicopathological parameters, higher incidence of disease progression, relapse, and poor overall survival.

Keywords

• Hodgkin disease
• Epstein-Barr virus infections
• Janus kinases
• NF kappa B