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已发表论文
基于中性粒细胞胞外诱捕网的风险模型和鉴别基因 LTF 在急性髓系白血病预后及免疫微环境调控中的作用研究
Authors Li Y, Zhang J, Liu T, Zhang D, Wang N, Liu X, Feng P, Zhang J, Ji C, Ye J
Received 23 August 2025
Accepted for publication 30 December 2025
Published 13 January 2026 Volume 2026:16 562651
DOI https://doi.org/10.2147/BLCTT.S562651
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Wilson Gonsalves
Yongjian Li,1,* Jingru Zhang,1– 3,* Tingting Liu,1 Di Zhang,1 Nana Wang,1 Xiaomin Liu,1 Panpan Feng,4 Juan Zhang,1 Chunyan Ji,1– 3 Jingjing Ye1– 3
1Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Shandong Key Laboratory of Hematological Diseases and Immune Microenvironment, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Hematological Diseases, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 4Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Jingjing Ye, Email yejingjing@sdu.edu.cn Chunyan Ji, Email jichunyan@sdu.edu.cn
Introduction: Dysregulation of neutrophil extracellular traps (NETs) formation is implicated in cancer progression, coagulation, and metastasis; however, the association with acute myeloid leukemia (AML) prognosis and the immune microenvironment remains poorly understood due to the inherent heterogeneity of NETs. This study aimed to elucidate the role of NETs-related genes in AML pathogenesis, risk stratification, and immune modulation.
Methods: We employed comprehensive bioinformatics approaches to analyze NETs-related gene expression profiles from cBioPortal, UCSC Xena, and Gene Expression Omnibus (GEO) databases. A prognostic model was constructed using 16 NETs-related gene signatures, with rigorous validation performed in both internal and external cohorts. Multivariate Cox regression analyses assessed the model’s independence as a prognostic indicator for overall survival (OS), and a clinical nomogram was developed for practical application. Additionally, immune cell infiltration and microenvironment characteristics were evaluated through enrichment analyses to correlate NETs activity with immunological features.
Results: The NETs-based prognostic model demonstrated robust predictive value for OS in AML patients across validation cohorts and was identified as an independent prognostic factor via multivariate Cox regression. This model enhanced existing risk stratification systems, with high NETs scores significantly associated with neutrophil enrichment and an immunosuppressive tumor microenvironment. Lactotransferrin (LTF) emerged as a pivotal NETs-related gene: its overexpression correlated strongly with adverse prognosis, poor chemotherapy response, and extensive remodeling of the immune landscape, including heightened neutrophil infiltration and immunosuppressive signatures.
Discussion: Our comprehensive analysis of NETs in AML suggests that NETs have a role in the tumor microenvironment and prognosis. LTF is a promising candidate biomarker of therapy response and prognostic prediction, which may contribute to individualized clinical decision-making. Further functional validation and prospective clinical studies are warranted to translate our observations into targeted interventions and refine risk-adapted treatment protocols.
Keywords: acute myeloid leukemia, neutrophil extracellular traps, prognosis, immune microenvironment, lactotransferrin
1Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 2Shandong Key Laboratory of Hematological Diseases and Immune Microenvironment, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Hematological Diseases, Qilu Hospital of Shandong University, Jinan, Shandong, People’s Republic of China; 4Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Jingjing Ye, Email yejingjing@sdu.edu.cn Chunyan Ji, Email jichunyan@sdu.edu.cn
Introduction: Dysregulation of neutrophil extracellular traps (NETs) formation is implicated in cancer progression, coagulation, and metastasis; however, the association with acute myeloid leukemia (AML) prognosis and the immune microenvironment remains poorly understood due to the inherent heterogeneity of NETs. This study aimed to elucidate the role of NETs-related genes in AML pathogenesis, risk stratification, and immune modulation.
Methods: We employed comprehensive bioinformatics approaches to analyze NETs-related gene expression profiles from cBioPortal, UCSC Xena, and Gene Expression Omnibus (GEO) databases. A prognostic model was constructed using 16 NETs-related gene signatures, with rigorous validation performed in both internal and external cohorts. Multivariate Cox regression analyses assessed the model’s independence as a prognostic indicator for overall survival (OS), and a clinical nomogram was developed for practical application. Additionally, immune cell infiltration and microenvironment characteristics were evaluated through enrichment analyses to correlate NETs activity with immunological features.
Results: The NETs-based prognostic model demonstrated robust predictive value for OS in AML patients across validation cohorts and was identified as an independent prognostic factor via multivariate Cox regression. This model enhanced existing risk stratification systems, with high NETs scores significantly associated with neutrophil enrichment and an immunosuppressive tumor microenvironment. Lactotransferrin (LTF) emerged as a pivotal NETs-related gene: its overexpression correlated strongly with adverse prognosis, poor chemotherapy response, and extensive remodeling of the immune landscape, including heightened neutrophil infiltration and immunosuppressive signatures.
Discussion: Our comprehensive analysis of NETs in AML suggests that NETs have a role in the tumor microenvironment and prognosis. LTF is a promising candidate biomarker of therapy response and prognostic prediction, which may contribute to individualized clinical decision-making. Further functional validation and prospective clinical studies are warranted to translate our observations into targeted interventions and refine risk-adapted treatment protocols.
Keywords: acute myeloid leukemia, neutrophil extracellular traps, prognosis, immune microenvironment, lactotransferrin