RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:The function of CD164 in breast cancer and its possibility as a molecular biomarker: bioinformatics analysis and experimental validation.
The function of CD164 in breast cancer and its possibility as a molecular biomarker: bioinformatics analysis and experimental validation.
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CD164 在乳腺癌进展中发挥关键作用,影响肿瘤生长、免疫逃逸和治疗反应。它代表了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。
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准靶向肿瘤特异性分子,提高治疗效果,同时将对健康组织的损伤降至最低。识别新的分子靶点对于改善乳腺癌的治疗效果和预后至关重要。
采用TCGA数据库评估CD164在乳腺癌中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实验、克隆形成实验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)以确定受CD164调控的通路。
CD164在乳腺癌组织中高表达,并与较差预后相关,包括较短的无病生存期和总生存期。化疗敏感性分析将CD164与多种靶向治疗的敏感性联系起来,提示其在致癌通路中的作用。免疫浸润分析显示,CD164与免疫抑制细胞相关,包括静息CD4记忆T细胞、M2巨噬细胞和肥大细胞,同时与Tregs和NK细胞呈负相关,强调了其在免疫抑制性肿瘤微环境中的重要意义。CD164敲低抑制了细胞活力和增殖,并诱导细胞周期阻滞和凋亡。RNA测序和GSEA显示,CD164调控增殖、代谢、迁移和黏附通路,同时抑制促肿瘤通路并激活免疫相关通路。
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.
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.
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.
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.
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