Perfil de expressão de genes inflamatórios no linfoma plasmablástico de cavidade oral

Abstract

Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin lymphoma that shows poor response to conventional chemotherapy regimens. Although genetic aberrations involving the JAK/STAT, RAS/RAF, NOTCH, IRF4, and MYC signalling pathways have been implicated in its pathogenesis, the therapeutic potential of targeting these pathways remains largely unexplored. Moreover, while most studies have focused on mutations related to tumour cell immortalisation, the role of cytokines, chemokines, growth factors, and intracellular signalling mediators in the PBL tumour microenvironment remains poorly characterised. This study aimed to investigate the immunomodulatory profile of PBL and its therapeutic potential, with a focus on inflammatory mediators and their associated signalling pathways. A total of 32 lymphoma cases were included: 10 PBLs, 11 diffuse large B-cell lymphomas not otherwise specified (DLBCL-NOS), and 11 plasma cell neoplasms (PCNs). Clinical data were collected retrospectively. EBV status was determined by chromogenic in situ hybridisation for EBER, and rearrangements involving MYC, BCL2, and BCL6 were assessed using fluorescence in situ hybridisation. Total RNA was extracted from formalin-fixed paraffin-embedded tissues, and the expression of 607 inflammation-related genes was analysed using the TaqMan™ OpenArray™ Human Inflammation Panel on the QuantStudio™ 12K Flex platform. Statistical and bioinformatic analyses were performed to identify differentially expressed genes, enriched signalling pathways, and protein–protein interaction networks. All lymphomas occurred in the oral cavity and presented predominantly as soft tissue swelling. Patients with PBL were younger and had shorter disease duration compared to the other groups. All PBL cases were positive for EBER, and half were HIV-positive. Triple rearrangements involving MYC, BCL2, and BCL6 were identified in one PBL and one DLBCL-NOS case. The inflammatory gene expression profile of PBL was more similar to DLBCL-NOS (r = 0.86) than to PCN (r = 0.78). Key differentially expressed genes included STAT4 and STAT5A (JAK-STAT pathway members), SOCS2 (a negative regulator of JAK-STAT), MAPK14 (a core component of the MAPK-ERK pathway), and BCL2A1, BCL6, BCL10, and NFKB1 (members or regulators of the NF-κB pathway). Interestingly, CR2/CD21, the EBV entry receptor, was underexpressed in PBL, while complement components C3 and C3AR1 were overexpressed. Enriched pathway analysis was consistent with these expression patterns. These findings highlight promising molecular candidates and support the potential role of complement inhibition as a novel therapeutic strategy for PBL.