ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1613529
This article is part of the Research TopicDeciphering Cell-Cell Interactions in Triple-Negative Breast CancerView all 3 articles
Identification of tumor associated neutrophils-related genes in triple-negative breast cancer for predicting prognosis and therapeutic response through integrated single-cell analysis
Provisionally accepted
- Wuxi People's Hospital, Wuxi, China
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Tumor-associated neutrophils (TANs) significantly influence tumor development, immune system suppression, and the spread of cancer in triple-negative breast cancer (TNBC). However, their molecular pathways and potential for therapy are not completely understood. We utilized Seurat and Harmony to perform quality control, batch correction, and cell annotation on single-cell RNA-seq data from TNBC patients (GSE222854). Comprehensive bioinformatics approaches-including immune infiltration analysis, GSEA, GSVA, drug sensitivity profiling, and ligand-receptor interaction network analysis were combined with functional validation (colony formation and Transwell assays) and clinical correlation studies via polychromatic immunofluorescence. Four TAN-associated genes (RASGRP4, TIMM10B, TNFRSF13C, and GRAP) with distinct roles in TNBC progression were identified. Functional assays revealed pro-tumorigenic effects of RASGRP4, TIMM10B, and GRAP, whereas TNFRSF13C exhibited tumor-suppressive properties.Clinically, elevated RASGRP4 and TIMM10B expression with reduced TNFRSF13C expression correlated with poor survival and accelerated disease progression, underscoring their prognostic significance. Our study revealed RASGRP4, TIMM10B, and TNFRSF13C as promising therapeutic targets in TNBC. Targeting these TAN-associated genes may disrupt pro-tumor immune responses, suggesting novel strategies to improve patient outcomes.
Keywords: Triple-negative breast cancer, immuno-regulation, metastasis, Single-cell transcriptional analysis, tumor associated neutrophils
Received: 17 Apr 2025; Accepted: 28 Aug 2025.
Copyright: © 2025 LI, Gong, Zhang, Yang, Xu, Wang and Hu. 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: Koukou LI, Wuxi People's Hospital, Wuxi, China
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