Neutrophil Elastase as a Prognostic Biomarker and Driver of Tumor Progression in Diffuse Large B‐Cell Lymphoma

INTRODUCTION: With increasing recognition of the prognostic role of neutrophils in malignancies, this study investigated the clinical significance of neutrophil elastase (NE) expression in diffuse large B-cell lymphoma (DLBCL). METHODS: ) groups, and the association between NE expression and prognosis was analyzed. In vitro experiments using SU-DHL-4 cells evaluated the effects of NE and the NE inhibitor sivelestat on cell proliferation, apoptosis, and the expression of apoptosis-related proteins. RESULTS: group. Patients with NE positivity had significantly shorter overall survival (OS) and progression-free survival (PFS) in the overall cohort, with similar findings in the non-GCB subgroup (p < 0.05). Univariate analysis identified LDH level, B symptoms, Ann Arbor stage, NE expression, IPI score, and treatment regimen as prognostic factors. Multivariate analysis confirmed elevated LDH, positive NE expression, IPI score > 2, and non-R-CHOP therapy as independent predictors of poor OS. In vitro, NE promoted SU-DHL-4 cell proliferation and suppressed apoptosis-related protein activation, whereas sivelestat inhibited proliferation, induced apoptosis, and reversed the effects of NE. CONCLUSION: NE expression is associated with an unfavorable prognosis in DLBCL and may serve as a potential prognostic biomarker. Moreover, NE promotes lymphoma cell proliferation and inhibits apoptosis, effects that can be effectively reversed by sivelestat.