ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1623511
Necrosis by sodium overload-associated genes TRPM4 and SLC9A1: biological roles and clinical implications in breast cancer progression
Provisionally accepted
- 1Harbin Medical University Cancer Hospital, Harbin, China
- 2Capital Medical University, No. 10 Xitoutiao, outside You'anmen, Fengtai District, Beijing, beijing, China
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Background: Breast cancer persists as a principal contributor to global cancer mortality, driven by heterogeneous molecular pathways. Necrosis by sodium overload, a recently characterized form of regulated cell death, remains underexplored in oncogenesis. This study investigates the pathobiological significance and therapeutic potential of NECSO-related genes in breast cancer, elucidating their mechanistic roles in tumor progression. Methods: Multi-omics analyses were performed using transcriptomic data from TCGA and GEO cohorts (n=1,217), we systematically evaluated seven NECSO-related genes. Advanced bioinformatics pipelines included differential expression analysis, immune subtype profiling, functional state correlation, protein interaction mapping, and survival analytics. Experimental validation involved immunohistochemical evaluation of clinical samples. Results: Through multi-omics analysis of GEO and TCGA cohorts, we identified two sodium homeostasis-related genes, TRPM4 and SLC9A1, as consistently upregulated oncogenes in breast cancer, with significant diagnostic and prognostic relevance. Functional in vitro assays demonstrated that knockdown of either gene not only suppressed proliferation, colony formation, migration, and induced apoptosis in breast cancer cells, but also led to reduced expression of the sodium-calcium exchanger NCX1. Conclusion: TRPM4 and SLC9A1 is a novel prognostic biomarker and potential therapeutic target in breast cancer. Dysregulated sodium homeostasis mediated by NECSO-related genes represents a targetable vulnerability in precision oncology.
Keywords: Sodium-induced cell death, breast cancer, biomarkers, Ion channel dysregulation, Immunohistochemistry
Received: 06 May 2025; Accepted: 17 Oct 2025.
Copyright: © 2025 Zhu, Guo, Su, Zhang, Lu, Zhang and Pang. 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: Hui Pang, panghui@hrbmu.edu.cn
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