ORIGINAL RESEARCH article
Front. Oncol.
Sec. Breast Cancer
This article is part of the Research TopicExploring the Breast Tumor Microenvironment: Association to Metastasis, Novel Risk Factors and Novel Treatments and Immunotherapies: Volume II.View all 14 articles
Leucine-Rich Repeat Neuronal 1 as a Prognostic Indicator and Functional Modulator in Breast Cancer
Provisionally accepted
- 1Shanghai Tenth People's Hospital, Tongji University, Shanghai, China
- 2Nanjing Medical University, Nanjing, China
- 3Qingdao University, Qingdao, China
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Advanced breast cancer remains a major therapeutic challenge with high mortality rates. While leucine-rich repeat (LRR) proteins play roles in various cancers including breast cancer, their specific functions are still underexplored. This study used databases like TCGA-BRCA, GEO, and UALCAN to investigate the expression of leucine-rich repeat neuronal (LRRN) family members in breast cancer, analyzed their clinical value, and identified LRRN1's prognostic significance in advanced cases. We found that LRRN1 is significantly downregulated in advanced breast cancer vs. normal tissues (p < 0.001), with High LRRN1 expression correlates with better disease-free survival (DFS) (HR = 0.755, 95% CI: 0.617–0.923, p < 0.01). Functional assays (proliferative, migratory, invasive) showed LRRN1 suppresses cancer cell metastasis without affecting proliferation (p<0.01). WGCNA, GO, KEGG analyses and western blot confirmed LRRN1 impacts the Wnt signaling pathway (p<0.05). Additionally, LRRN1 may activate γδ T cells and resting dendritic cells, regulate M1/M2 macrophage balance in the tumor microenvironment (p<0.001), and mediate the efficacy of certain tyrosine kinase inhibitors (TKIs) (p<0.001). Overall, LRRN1 is a promising prognostic indicator and functional mediator in advanced breast cancer, potentially influencing Wnt signaling and regulating immunotherapy responses, though its mechanisms and clinical applications require further exploration.
Keywords: Leucine-Rich Repeat Neuronal 1, breast cancer, metastasis, Wnt signals, Immunotherapy
Received: 14 Oct 2025; Accepted: 19 Nov 2025.
Copyright: © 2025 Wang, Zhou, Ping, Lu, Zhang, Song, Zhao 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:
Hongming Song, hongmingsong@qdu.edu.cn
Junyong Zhao, 1610705@tongji.edu.cn
Dengfeng Li, 711ldf@tongji.edu.cn
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