Zhang Ying, Guo Wei, Wang Haotian, Zhan Zhumei, Xing Rui, Bai Ou
Department of Hematology, The First Hospital of Jilin University, Changchun, China.
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
iScience. 2025 Jul 28;28(9):113225. doi: 10.1016/j.isci.2025.113225. eCollection 2025 Sep 19.
Hepatitis B virus X protein (HBx) is implicated in the pathogenesis of diffuse large B cell lymphoma (DLBCL). In this study, HBx-stably overexpressing DLBCL cell lines and mouse xenograft models were established to investigate HBx-driven transcriptional changes and functional effects. HBx enhanced cell proliferation, migration, and invasion and altered cell cycle progression. Transcriptomic analysis of tumor tissues revealed distinct gene expression profiles. Integrative analyses, including differential expression, WGCNA, and LASSO regression, identified five HBx-associated hub genes. Among these, was consistently upregulated in a large DLBCL patient cohort and associated with poorer overall survival. Elevated expression was confirmed in HBx-overexpressing cells. These findings highlight as a potential biomarker or therapeutic target in HBV-related DLBCL. This study provides a multi-omics framework integrating and models to elucidate the viral contribution to lymphoma progression.
乙型肝炎病毒X蛋白（HBx）与弥漫性大B细胞淋巴瘤（DLBCL）的发病机制有关。在本研究中，建立了稳定过表达HBx的DLBCL细胞系和小鼠异种移植模型，以研究HBx驱动的转录变化和功能影响。HBx增强了细胞增殖、迁移和侵袭，并改变了细胞周期进程。肿瘤组织的转录组分析揭示了不同的基因表达谱。包括差异表达、WGCNA和LASSO回归在内的综合分析确定了五个与HBx相关的枢纽基因。其中，在一大群DLBCL患者中持续上调，并与较差的总生存期相关。在过表达HBx的细胞中证实了该基因表达升高。这些发现突出了该基因作为HBV相关DLBCL潜在生物标志物或治疗靶点的作用。本研究提供了一个整合细胞系和小鼠模型的多组学框架，以阐明病毒对淋巴瘤进展的影响。
