[Correlation between neutrophil extracellular traps and clinicopathological characteristics and prognosis of EGFR wild-type lung adenocarcinoma].

Objective: To investigate the predictive value of neutrophil extracellular traps (NETs) on the prognosis of patients with epidermal growth factor receptor (EGFR) wild-type lung adenocarcinoma. Methods: A total of 132 surgical paraffin specimens of EGFR wild-type lung adenocarcinoma diagnosed at the Tumor Hospital Affiliated to Xinjiang Medical University from January 2016 to December 2023 and 12 pairs of cancer and paracancerous fresh tissues from patients with EGFR wild-type lung adenocarcinoma diagnosed in March-July 2024 were collected with their clinical information. Western blotting and immunofluorescence were used to detect the expression levels of citrullinated histone H3 (CitH3) and myeloperoxidase (MPO) in cancerous and paraneoplastic tissues. Immunohistochemistry was used to detect the infiltration of PD-L1, CD4⁺ T cells and CD8⁺ T cells in the tumors. The clinical and prognostic correlations between NETs and EGFR wild-type lung adenocarcinoma patients were analyzed. Results: The expression of MPO (P＜0.001) and CitH3 (P=0.009) was significantly increased in the tumors compared with the paracancerous tissues. The rate of high expression of NETs in cancer tissues was higher in patients with EGFR wild-type lung adenocarcinoma who were in stage Ⅲ and Ⅳ, with lymph node metastasis, distant metastasis, pleural invasion, high expression of Ki-67, low expression of CD8⁺ T, and lowered lymphocyte counts when compared to paraneoplastic tissues (P＜0.05). Patients were stratified based on TNM stage Ⅱb for prognostic analysis. Kaplan-Meier univariate analysis showed that the median overall survival (OS) (stage Ⅰ to Ⅱb: 47 vs 87 months; stage Ⅲ to Ⅳ: 27 vs not reach) and the median disease-free survival (DFS) (stage Ⅰ to Ⅱb: 42 vs 78 months; stage Ⅲ to Ⅳ: 18 vs 39 months) of patients with high expression of NETs in stage Ⅰ to II b and stage Ⅲ to Ⅳ were lower than those with low expression (stage Ⅰ to Ⅱb: OS, P＜0.001; DFS, P＜0.001; stage Ⅲ to Ⅳ: OS, P=0.001; DFS, P=0.022). Multivariate Cox regression analysis also showed that the OS (stage Ⅰ to Ⅱb: HR=3.513 [95% CI, 1.966-6.277], P＜0.001; stage Ⅲ to Ⅳ: HR=3.215 [95% CI, 1.324-7.806], P=0.010) and the DFS (stage Ⅰ to Ⅱb: HR=2.478 [95% CI, 1.396-4.400], P=0.002; stage Ⅲ to Ⅳ: HR=2.248 [95% CI, 1.089-4.638], P=0.028) in the group with high expression of NETs in either stage I to Ⅱb or stage Ⅲ to Ⅳ were significantly shorter than those in the group with low expression. Conclusion: The EGFR wild-type lung adenocarcinoma patients with high expression of NETs have relatively shorter DFS and OS, which are independent risk factors for the prognosis of patients with EGFR wild-type lung adenocarcinoma, and are likely to be the potential biomarkers for the diagnosis and treatment of EGFR wild-type lung adenocarcinoma.