EBV promotes tumorigenicity and worsens the prognosis of Hodgkin lymphoma through the expression of survival enhancing proteins by activating the JAK / STAT and NF-kB signaling pathways. (A comparative study between EBV positive and negative Hodgkin lymphoma)

Background: Epstein-Barr virus (EBV) is involved in 40% of all Hodgkin's lymphoma (HL) cases. EBV produces epigenetic alterations in the host genome that decrease the expression of proapoptotic proteins and activate the expression of survival immortalization genes. Methods According to EBNA-1 detection by nested PCR, 64 patients with HL were classified into two groups: EBV positive and negative HL. The expression levels of JAK/STAT and NF-kB pathway mRNA molecules (JAK2, STAT1, IRF-1, PD-L1, IFN-, NFkB, Bcl-xL, and COX-2) by both RT-PCR and qRT-PCR, and the results proteins PD-L1, Bcl-xL, and COX-2 by immunohistochemistry were analyzed and correlated with each other, Results Positive mRNA expression of either (JAK/STAT) or (NF-kB) pathways: (JAK2, STAT1, IRF-1, and PD-L1) and (IFN-, NFkB, Bcl-xL, COX-2) respectively are highly significantly correlated with each other (p 0.001) and with EBV positive HL patients (p 0.001). EBV positive HL cases had a higher incidence of relapse (p = 0.008), poor DFS (p = 0.013), higher mortality (p = 0.015), and low OS rates (p 0.028) Conclusion EBV in HL promotes the expression of survival immortalization signals by activating the JAK/STAT and NF-kB pathways and is associated with poor clinicopathological criteria, a higher incidence of disease progression, relapse, and poor overall survival. Therefore, targeting the JAK/STAT and NF-kB pathway members could be valuable in the management of EBV-associated Hodgkin's Lymphoma cases.