Abstract
Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease that requires more reliable prognostic biomarkers. In this study, bioinformatic analysis identified replication factor C 5 (RFC5), one of the DNA repair-related gene, as a potential novel oncogene in DLBCL. Analysis of public datasets and immunohistochemical staining showed that RFC5 expression was significantly higher in tumor samples than in normal samples. High RFC5 expression was associated with worse prognostic clinical features. Notably, there was a difference in overall survival (OS) between the high- and low-RFC5 expression groups. Multivariate Cox regression analyses showed that RFC5 was an independent risk factor associated with poorer OS. Furthermore, correlations were observed between RFC5 expression in DLBCL and TIME(Tumor Immune Microenvironment), as well as immune cell infiltration, cytokine levels, cytokine receptor expression, and immune checkpoint activity. Gene set enrichment analysis (GSEA) analysis revealed that the elevated RFC5 expression group showed significant enrichment in multiple tumor signaling pathways. These results suggest that RFC5 may contribute to the pathogenesis of DLBCL by modulating these critical molecular pathways. Our findings indicate that RFC5 may be a novel prognostic biomarker for DLBCL. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12672-025-04199-z.