ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1467357
This article is part of the Research TopicAdvancing Immunotherapy: Machine Learning and AI in Tumor Microenvironment AnalysisView all 3 articles
Tumor associated neutrophils promote prostate cancer progression by mediating neutrophil trap secretion through PSMA1-NF-κB-HIF-1α signaling axis
Provisionally accepted
- First Hospital of Lanzhou University, Lanzhou, China
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Prostate cancer (PCa) is a common and deadly cancer in men, and despite its low specificity, PSA testing is the main method that is used to predict prognosis. Effective methods for predicting prognosis in clinical practice are lacking. Here, ① in this retrospective analysis of clinical data of PCa patients, we discovered that patients with PCa have elevated neutrophil levels and a greater risk of complications than patients with prostatic hyperplasia. ② We integrated LASSO regression analysis and machine learning analyses to create a prognostic prediction model involving 6 genes, and this model effectively categorized patients into high-risk and low-risk groups, with higher risk scores indicating a poorer prognosis. Furthermore, we used multivariate regression analysis to confirm that the risk score was an independent prognostic factor and created nomograms on the basis of clinical characteristics. Notably, the deconvolution algorithm revealed different compositions of the tumor microenvironment, with a greater proportion of neutrophils observed in the high-risk group. ③ Finally, we conducted single-cell sequencing analysis and established a prostate cancer organoid model to confirm that TANs may exacerbate the TME in PCa via neutrophil trap formation, which is mediated by the PSMA1-NF-κB-HIF-1α signaling axis. Overall, this novel NET-related signature of PCa provides new insights for in-depth understanding and prediction of PCa prognosis.
Keywords: prostate cancer, Neutrophil extracellular trap, Prognostic signature, Neutrophil, organoid cell culture
Received: 19 Jul 2024; Accepted: 17 Jul 2025.
Copyright: © 2025 Dai, Wang, Huang, Jiang, Yuan, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xun Li, First Hospital of Lanzhou University, Lanzhou, China
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