mzb1驱动的内质网应激模型作为乳腺癌进展和生存的预测因子

IF 3.1 4区 生物学 Q1 GENETICS & HEREDITY
Purong Zhang, Rui Wang, Yuying Wang, Ning Zhang, Ke Luo
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引用次数: 0

摘要

内质网(ER)应激及其相关的未折叠蛋白反应(UPR)已被证明在癌症的进展中起着至关重要的作用,但它们在乳腺癌(BC)中的预后意义尚不清楚。在这项研究中,开发了一个可靠的er相关基因标记,用于预测BC预后和研究相关的免疫景观。通过利用公共数据集和分析方法,我们开发了16个er相关基因风险标记,并验证了其在独立患者群体中预测预后的有效性。高危组患者的生存率明显较低。单细胞分析显示,低风险组表现出更强的免疫相互作用。相反,表现出免疫检查点升高的高危人群可能意味着免疫抑制微环境或对免疫检查点抑制剂治疗的敏感性提高。体外和体内实验证实,下调Marginal Zone B和B1 Cell Specific Protein (MZB1)的表达可显著抑制乳腺癌的增殖、侵袭和肿瘤发生。16种er相关基因标记能够有效地将乳腺癌患者划分为不同的风险水平,从而为个性化治疗提供依据。MZB1已被确定为一个重要的调节因子,表明其作为乳腺癌治疗靶点的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MZB1-Driven Endoplasmic reticulum stress model as a predictor of breast cancer progression and survival

Endoplasmic reticulum (ER) stress and its associated unfolded protein response (UPR) have been demonstrated to play a crucial role in cancer’s progression, but their prognostic significance in breast cancer (BC) remains unclear. In this study, a reliable ER-related gene signature was developed for the purpose of predicting BC prognosis and investigating the associated immune landscape. By utilizing public datasets and analytical methods, we developed a 16 ER-related gene risk signature and verified its efficacy in predicting prognosis in independent patient groups. Patients in the high-risk group exhibited significantly poorer survival rates. Single-cell analysis revealed that the low-risk group exhibited stronger immune interactions. Conversely, the high-risk group exhibiting elevated immune checkpoints may signify an immunosuppressive microenvironment or heightened sensitivity to immune checkpoint inhibitor therapy. In vitro and vivo experiments confirmed that knocking down the expression of Marginal Zone B And B1 Cell Specific Protein (MZB1) significantly inhibited the proliferation, invasion, and tumorigenesis of breast cancer. The 16 ER-related gene signature is capable of effectively categorizing breast cancer patients into different risk levels, thereby providing a basis for personalized therapy. MZB1 has been identified as a significant regulatory factor, suggesting its potential as a target for the treatment of breast cancer.

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来源期刊
CiteScore
3.50
自引率
3.40%
发文量
92
审稿时长
2 months
期刊介绍: Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?
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