Breast cancer (BC) stands as a prominent contributor to global cancer-related mortality, with an increasing incidence annually. This study aims to investigate AGRN gene expression in BC, as well as explore its influence on the tumor immune microenvironment. AGRN displayed a pronounced upregulation in BC tissues relative to paracancerous tissues. Single-cell RNA analysis highlighted AGRN-specific elevation within cancer cell clusters and also showed expression expressed in stromal as well as immune cell clusters. AGRN upregulation was positively correlated with clinicopathological stage and negatively correlated with BC prognosis. As revealed by the in vitro experiment, AGRN knockdown effectively hinders BC cells in terms of proliferation, invasion as well as migration. AGRN protein, which may interact with EXT1, LRP4, RAPSN, etc., was primarily distributed in the cell cytoplasm. Notably, immune factors might interact with AGRN in BC, evidenced by its discernible associations with immunofactors like IL10, CD274, and PVRL2. Mass spectrometry and immunohistochemistry revealed that the reduction of AGRN led to an increase in CD8⁺ T cells with triple-negative breast cancer (TNBC). Mechanistically, the connection between TRIM7 and PD-L1 is improved by AGRN, acting as a scaffold, thereby facilitating the accelerated degradation of PD-L1 by TRIM7. Downregulation of AGRN inhibits BC progression and increases CD8⁺ T cell recruitment. Targeting AGRN may contribute to BC treatment. The biomarker AGRN, serving as a therapeutic target for BC, emerges as a prospective avenue for enhancing both diagnosis and prognosis in BC cases.

中文翻译：

---

抑制 AGRN 可增强 CD8+ T 细胞募集并抑制乳腺癌进展

乳腺癌（BC）是全球癌症相关死亡率的一个重要因素，发病率逐年上升。本研究旨在探讨AGRN基因在BC中的表达，并探讨其对肿瘤免疫微环境的影响。相对于癌旁组织，AGRN 在 BC 组织中表现出明显的上调。单细胞 RNA 分析强调了癌细胞簇内 AGRN 特异性的升高，并且还显示了基质细胞和免疫细胞簇中的表达。 AGRN 上调与临床病理分期呈正相关，与 BC 预后呈负相关。体外实验表明，AGRN敲低有效阻碍BC细胞的增殖、侵袭和迁移。 AGRN蛋白主要分布在细胞质中，可能与EXT1、LRP4、RAPSN等相互作用。值得注意的是，免疫因子可能与 BC 中的 AGRN 相互作用，其与 IL10、CD274 和 PVRL2 等免疫因子的明显关联证明了这一点。质谱和免疫组织化学显示，AGRN 的减少导致三阴性乳腺癌 (TNBC) 中CD8 ⁺ T 细胞的增加。从机制上讲，AGRN 改善了 TRIM7 和 PD-L1 之间的连接，充当支架，从而促进 TRIM7 加速降解 PD-L1。 AGRN 的下调可抑制 BC 进展并增加 CD8 ⁺ T 细胞募集。靶向 AGRN 可能有助于 BC 治疗。生物标志物 AGRN 作为 BC 的治疗靶点，成为增强 BC 病例诊断和预后的前瞻性途径。