Biomedical informatics analysis has revealed a novel hub gene of the HBx in the pathogenesis and progression of DLBCL.

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 in vitro 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, NTN1 was consistently upregulated in a large DLBCL patient cohort and associated with poorer overall survival. Elevated NTN1 expression was confirmed in HBx-overexpressing cells. These findings highlight NTN1 as a potential biomarker or therapeutic target in HBV-related DLBCL. This study provides a multi-omics framework integrating in vivo and in vitro models to elucidate the viral contribution to lymphoma progression.