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

IF 1.6 Q2 MEDICINE, GENERAL & INTERNAL Iranian Journal of Medical Sciences Pub Date : 2024-02-01 DOI:10.30476/IJMS.2023.97287.2896
Mohamed Ali Alabiad, Warda M M Said, Rema H Faraj Saad, Rawda Balata, Asmaa A Mahmoud, Elsayed Anany Metwally, Amany Mohamed Shalaby, Walaa Samy, Ahmed M Yehia, Amar Ibrahim Omar Yahia, Mohammed Alorini, Doaa I Abdelrahman
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引用次数: 0

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. A preprint of this manuscript is available on research square (doi: 10.21203/rs.3.rs-1857436/v1).

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Epstein-Barr 病毒通过激活 JAK/STAT 和 NF-κB 信号通路促进肿瘤致病性并恶化霍奇金淋巴瘤预后
背景:40%的霍奇金淋巴瘤(HL)患者体内可检测到爱泼斯坦-巴尔病毒(EBV)。在潜伏期,EBV会诱导宿主基因组发生表观遗传学改变,并降低促凋亡蛋白的表达。本研究旨在评估EBV阳性和阴性经典型霍奇金淋巴瘤(CHL)患者中JAK/STAT和NF-κB通路的mRNA分子和蛋白终产物的表达水平及其与临床病理和预后参数的关系:一项前瞻性队列研究于2017年至2022年在埃及扎加齐格大学医院医学院(埃及扎加齐格)进行。64 名 CHL 患者的活检样本被分为 EBV 阳性组和 EBV 阴性组。研究人员测定了 mRNA 分子(JAK2、STAT1、IRF-1、PD-L1、IFN-γ、NF-κB、Bcl-xL、COX-2)和蛋白质终产物(PD-L1、Bcl-xL、COX-2)的表达水平,并将其与临床病理和预后参数进行了比较。数据采用Chi square检验和Kaplan-Meier估计法进行分析:结果:EBV 阳性的 CHL 患者与 mRNAs 分子(PC)的阳性表达明显相关:通过激活JAK/STAT和NF-κB信号通路,EBV阳性CHL与不良的临床病理参数、较高的疾病进展发生率、复发率和较差的总生存率相关。本稿件的预印本可在研究广场(doi: 10.21203/rs.3.rs-1857436/v1)上查阅。
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来源期刊
Iranian Journal of Medical Sciences
Iranian Journal of Medical Sciences MEDICINE, GENERAL & INTERNAL-
CiteScore
3.20
自引率
0.00%
发文量
84
审稿时长
12 weeks
期刊介绍: The Iranian Journal of Medical Sciences (IJMS) is an international quarterly biomedical publication, which is sponsored by Shiraz University of Medical Sciences. The IJMS intends to provide a scientific medium of com­muni­cation for researchers throughout the globe. The journal welcomes original clinical articles as well as clinically oriented basic science re­search experiences on prevalent diseases in the region and analysis of various regional problems.
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