Inflammatory gene expression profile of oral plasmablastic lymphoma

Plasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma with a poor prognosis and short survival rates. It is classified as a large B-cell lymphoma subtype, but carries a plasmacytic immunophenotype. Therefore, PBL has pathogenetic overlaps with diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) and plasma cell neoplasms (PCNs). Although recent studies have characterized important genetic abnormalities in PBL, the precise molecular mechanisms driving its pathogenesis remain elusive. In this study, we analyzed 607 inflammatory genes in 10 PBL, 11 DLBCL NOS/high-grade B-cell lymphoma (DLBCL NOS/HGBCL), and 11 PCN samples to uncover the PBL immunoregulatory landscape and to identify promising therapeutic target candidates. Several differentially expressed genes were observed, including STAT4, STAT5A, and MAPK14, with enriched pathways such as JAK-STAT, nuclear factor-kappa B (NF-κB), and complement signaling in the PBL group. Notably, CR2 was underexpressed in PBL compared to DLBCL NOS/HGBCL and PCNs, suggesting a restricted Wp latency stage of Epstein-Barr virus (EBV), which may contribute to immune evasion. Functional analyses identified key immune pathways, including cytokine-receptor interactions, Toll-like receptor signaling, and neutrophil extracellular trap formation, with protein-protein interaction networks, emphasizing complement activation and JAK-STAT signaling pathways. In conclusion, oral PBL exhibits a complex inflammatory gene expression profile, and key signaling pathways, particularly JAK-STAT, NF-κB, and complement activation, are enriched in this tumor compared to DLBCL NOS/HGBCL and PCNs.