Zhang Purong, Wang Rui, Wang Yuying, Zhang Ning, Luo Ke
Department of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Sichuan, Chengdu, China.
College of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, China.
Funct Integr Genomics. 2025 Aug 29;25(1):179. doi: 10.1007/s10142-025-01676-0.
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.
内质网（ER）应激及其相关的未折叠蛋白反应（UPR）已被证明在癌症进展中起关键作用，但其在乳腺癌（BC）中的预后意义仍不清楚。在本研究中，为预测BC预后和研究相关免疫格局，开发了一种可靠的ER相关基因特征。通过利用公共数据集和分析方法，我们开发了一个16个ER相关基因的风险特征，并在独立患者组中验证了其预测预后的有效性。高危组患者的生存率显著较差。单细胞分析显示，低危组表现出更强的免疫相互作用。相反，高危组免疫检查点升高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增加。体外和体内实验证实，敲低边缘区B细胞和B1细胞特异性蛋白（MZB1）的表达可显著抑制乳腺癌的增殖、侵袭和肿瘤发生。16个ER相关基因特征能够有效地将乳腺癌患者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。
