Multi-omics analysis of NET+ TAN explains the immunosuppressive TME and prognosis value of malignant clinical characteristics in TNBC

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2026-04-01 Epub Date: 2026-02-10 DOI:10.1016/j.tranon.2026.102692

Qiannan Zhu , Xiangxin Zheng , Xiaochao Zhu , Peng Yang , Mengzhu Yang

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引用次数: 0

Abstract

Triple-negative breast cancer (TNBC) continues to exhibit a poor response to both immunotherapy and endocrine therapy, primarily due to its complex genetic heterogeneity and tumor immune microenvironment (TIME). Neutrophil extracellular traps (NETs) are involved in neutrophil development and degranulation in treatment-resistant tumors, particularly TNBC and metastatic cases. Using a combination of single-cell RNA sequencing (scRNA-seq) datasets, bulk mRNA sequencing data from The Cancer Genome Atlas (TCGA) cohort, microarray data from the METABRIC and GEO databases, and epigenetic sequencing resources, we comprehensively investigated the functional characteristics and prognostic potential of NET-positive tumor-associated neutrophils (NET+ TAN) in TNBC. A six-gene panel derived from NET+ TAN has been identified as a reliable diagnostic biomarker for the survival of patients with TNBC and has been validated across several independent cohorts. Notably, our findings indicate that NET+ TAN facilitate T cell reprogramming in TNBC, thereby establishing a suppressive TIME and promoting tumor progression. This study provides a comprehensive perspective on the significance of NETs in patients with TNBC, with the aim of offering genetic and epigenetic insights into the mechanisms by which NETs may transition from cold to hot tumor phenotype, as well as valuable recommendations for therapeutic strategies.

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NET+ TAN的多组学分析解释了TNBC恶性临床特征的免疫抑制TME及预后价值。

三阴性乳腺癌（TNBC）继续表现出对免疫治疗和内分泌治疗的不良反应，主要是由于其复杂的遗传异质性和肿瘤免疫微环境（TIME）。中性粒细胞胞外陷阱（NETs）参与治疗耐药肿瘤的中性粒细胞发育和脱颗粒，特别是TNBC和转移病例。利用单细胞RNA测序（scRNA-seq）数据集、来自癌症基因组图谱（TCGA）队列的大量mRNA测序数据、来自METABRIC和GEO数据库的微阵列数据以及表观遗传测序资源，我们全面研究了TNBC中NET阳性肿瘤相关中性粒细胞（NET+ TAN）的功能特征和预后潜力。NET+ TAN衍生的六基因组已被确定为TNBC患者生存的可靠诊断生物标志物，并已在多个独立队列中得到验证。值得注意的是，我们的研究结果表明，NET+ TAN促进TNBC中T细胞重编程，从而建立抑制时间并促进肿瘤进展。本研究对NETs在TNBC患者中的意义提供了一个全面的视角，旨在为NETs从冷肿瘤表型向热肿瘤表型转变的机制提供遗传学和表观遗传学的见解，并为治疗策略提供有价值的建议。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.