Neuro-related gene signatures predict prognosis in diffuse large B-Cell lymphoma and uncover TRPV2-mediated tumor microenvironment regulation.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous malignancy. Although the R-CHOP regimen has significantly improved the prognosis for most patients, a subset continues to experience poor therapeutic outcomes. Recent studies have highlighted the role of the nervous system in cancer, yet its impact on DLBCL remains unclear. In this study, 21 neuro-related (NR) genes were identified from the Gene Ontology database, and a prognostic risk scoring model for DLBCL was developed and validated across multiple cohorts. The NR-based score effectively stratified patients according to survival outcomes. The high NR score group was characterized by an immunosuppressive microenvironment, activation of pro-proliferative pathways, and increased mutation frequencies of oncogenes such as TP53 and MYC. In contrast, the low NR score group exhibited enriched inflammatory responses and immune activation signals. The key gene TRPV2, associated with favorable prognosis, was found to promote M1-like polarization in monocytes/macrophages and enhance antigen presentation in B cells. This study establishes the NR risk score as a novel prognostic tool for DLBCL and underscores neuro-immune interactions as potential therapeutic targets.