Fu Chen, Hu Yanyun, Yang Lei, Sun Weifeng
Pharmaceutical Sciences Laboratory Center, School of Pharmacy, China Medical University, Shenyang, 110122, People's Republic of China.
Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, 110122, People's Republic of China.
Discov Oncol. 2025 Jun 8;16(1):1030. doi: 10.1007/s12672-025-02832-5.
The immune response can be modulated by autophagy to alter tumor growth. SERPINA1 is not only an autophagy-related protein but also a serine protease inhibitor with the potential for immunotherapy and targeted drug therapy.
Based on the latest multi-omic databases, we evaluated SERPINA1 mRNA and protein expression levels, prognostic value, methylation and mutation, signaling pathway, and gene ontology analysis and explored their relevance. The relationship between SERPINA1 expression and immune and drug sensitivity was also analyzed. Single-cell sequencing was used to validate the function and immunity in different cancers.
Many tumors are associated with abnormal SERPINA1 expression and a poor prognosis. According to our study, DNA methylation, gene mutations, and post-translational modifications of SERPINA1 were significantly and positively correlated with its expression levels in breast cancer as a diagnostic marker. In addition, we observed that SERPINA1 positively correlates with macrophages and was able to stimulate M2 macrophage polarization. It was found that SERPINA1 was associated with macrophages in glioma immune microenvironments.
Considering that SERPINA1 plays a role in cancer progression, SERPINA1 may be a new promising target for immunotherapy and drug target therapy.
免疫反应可通过自噬进行调节,从而改变肿瘤生长。丝氨酸蛋白酶抑制剂A1(SERPINA1)不仅是一种自噬相关蛋白,还是一种具有免疫治疗和靶向药物治疗潜力的丝氨酸蛋白酶抑制剂。
基于最新的多组学数据库,我们评估了SERPINA1的mRNA和蛋白质表达水平、预后价值、甲基化和突变情况、信号通路以及基因本体分析,并探讨了它们之间的相关性。还分析了SERPINA1表达与免疫及药物敏感性之间的关系。利用单细胞测序验证其在不同癌症中的功能和免疫情况。
许多肿瘤与SERPINA1表达异常及预后不良相关。根据我们的研究,SERPINA1的DNA甲基化、基因突变和翻译后修饰与其在乳腺癌中的表达水平显著正相关,可作为诊断标志物。此外,我们观察到SERPINA1与巨噬细胞呈正相关,并且能够刺激M2巨噬细胞极化。研究发现SERPINA1与胶质瘤免疫微环境中的巨噬细胞有关。
鉴于SERPINA1在癌症进展中发挥作用,它可能是免疫治疗和药物靶向治疗的一个新的有前景的靶点。