Epstein-Barr Virus Promotes Tumorigenicity and Worsens Hodgkin Lymphoma Prognosis by Activating JAK/STAT and NF-κB Signaling Pathways
نویسندگان
1 Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
2 Department of Clinical Oncology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
3 Department of Medical Oncology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
4 Hematology Unit, Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt
5 Department of General Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt
6 Department of Basic Medical Sciences, College of Medicine, University of Bisha, Bisha, Saudi Arabia
7 Department of Pathology, Faculty of Medicine and Health Sciences, University of Kordofan, Elobeid, Sudan
8 Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi, Libya
9 Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi, Libya
10 Hematology Unit, Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt
11 Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Zagazig University, Zagazig, Egypt
12 Department of Basic Medical Sciences, Unaizah College of Medicine and Medical Sciences, Qassim University, Unaizah, Kingdom of Saudi Arabia
doi
10.30476/ijms.2023.97287.2896چکیده
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.
