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

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).

Eighty-seven patients with newly diagnosed primary DLBCL treated at Yancheng First People's Hospital between June 2020 and September 2024 were included. NE expression in tumor tissues was assessed by immunohistochemistry. Clinical and pathological characteristics were compared between NE-positive (NE⁺) and NE-negative (NE^-) 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.

Positive NE expression was detected in 51.7% of DLBCL specimens. Compared with the NE^- group, the NE⁺ group showed a higher proportion of patients with International Prognostic Index (IPI) scores > 2 and intermediate-high/high-risk Ann Arbor stages. Ki-67 expression was also elevated in the NE⁺ 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.

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.