Li Mengxin, Mao Juanjuan, Wang Guang, Chen Jiasi, Hong Jinghui, Wang Xue, Liang Baoling, Song Dong
Department of Breast Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, China.
Department of Biomedical Science, College of Basic Medical Sciences, Jilin University, Changchun, China.
Front Immunol. 2025 Jul 7;16:1601547. doi: 10.3389/fimmu.2025.1601547. eCollection 2025.
BACKGROUND: Breast cancer is the most prevalent malignancy among women globally. Molecular-targeted therapy improves treatment efficacy by precisely targeting tumor-specific molecules, minimizing damage to healthy tissues. Identifying new molecular targets is essential for enhancing therapeutic outcomes and prognosis in breast cancer. METHODS: The TCGA database was used to assess CD164 expression in breast cancer and its correlation with prognosis. Chemosensitivity analysis was performed to evaluate the association between CD164 and response to targeted therapies. Immune infiltration analysis was conducted to assess the relationship between CD164 expression and immune cell populations. CCK-8 assays, clonogenic assays, and flow cytometry analyses were employed to examine the effects of CD164 knockdown on cell viability, proliferation, cell cycle progression, and apoptosis. RNA sequencing and Gene Set Enrichment Analysis (GSEA) were performed to identify pathways regulated by CD164. RESULTS: CD164 was highly expressed in breast cancer tissues and correlated with poorer prognosis, including shorter disease-free and overall survival. Chemosensitivity analysis linked CD164 to sensitivity to multiple targeted therapies, suggesting its role in oncogenic pathways. Immune infiltration analysis revealed CD164's association with immunosuppressive cells, including resting CD4 memory T cells, M2 macrophages, and mast cells, while exhibiting a negative correlation with Tregs and NK cells, underscoring its significance in the immunosuppressive tumor microenvironment. CD164 knockdown inhibited cell viability and proliferation and induced cell cycle arrest and apoptosis. RNA sequencing and GSEA showed that CD164 regulates proliferation, metabolism, migration, and adhesion pathways while suppressing tumor-promoting pathways and activating immune-related pathways. CONCLUSIONS: CD164 plays a critical role in breast cancer progression, influencing tumor growth, immune evasion, and therapeutic response. It represents a promising therapeutic target, offering potential for improving breast cancer treatment and prognosis.
背景：乳腺癌是全球女性中最常见的恶性肿瘤。分子靶向治疗通过精确靶向肿瘤特异性分子来提高治疗效果，最大限度地减少对健康组织的损害。识别新的分子靶点对于改善乳腺癌的治疗结果和预后至关重要。 方法：使用TCGA数据库评估乳腺癌中CD164的表达及其与预后的相关性。进行化疗敏感性分析以评估CD164与靶向治疗反应之间的关联。进行免疫浸润分析以评估CD164表达与免疫细胞群体之间的关系。采用CCK-8测定、克隆形成测定和流式细胞术分析来检测CD164敲低对细胞活力、增殖、细胞周期进程和凋亡的影响。进行RNA测序和基因集富集分析（GSEA）以识别受CD164调控的通路。 结果：CD164在乳腺癌组织中高表达，与较差的预后相关，包括无病生存期和总生存期较短。化疗敏感性分析将CD164与对多种靶向治疗的敏感性联系起来，表明其在致癌途径中的作用。免疫浸润分析显示CD164与免疫抑制细胞有关，包括静息CD4记忆T细胞、M2巨噬细胞和肥大细胞，同时与调节性T细胞和自然杀伤细胞呈负相关，突出了其在免疫抑制肿瘤微环境中的重要性。CD164敲低抑制细胞活力和增殖，并诱导细胞周期停滞和凋亡。RNA测序和GSEA表明，CD164调节增殖、代谢、迁移和黏附通路，同时抑制肿瘤促进通路并激活免疫相关通路。 结论：CD164在乳腺癌进展中起关键作用，影响肿瘤生长、免疫逃逸和治疗反应。它是一个有前景的治疗靶点，为改善乳腺癌治疗和预后提供了潜力。
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