Joint Laboratory for Translational Medicine Research, Liaocheng People's Hospital, Liaocheng, 252000, China.
Sci Rep. 2022 Jun 22;12(1):10567. doi: 10.1038/s41598-022-14575-2.
Netrin-4 (NTN4), a member of neurite guidance factor family, can promote neurite growth and elongation. This study aims to investigate if NTN4 correlates with prognosis and immune infiltration in breast cancer. The prognostic landscape of NTN4 and its relationship with immune infiltration in breast cancer were deciphered with public databases and immunohistochemistry (IHC) in tissue samples. The expression profiling and prognostic value of NTN4 were explored using UALCAN, TIMER, Kaplan-Meier Plotter and Prognoscan databases. Based on TIMER, relationships of NTN4 expression with tumor immune invasion and immune cell surface markers were evaluated. Transcription and survival analyses of NTN4 in breast cancer were investigated with cBioPortal database. The STRING database was explored to identify molecular functions and signaling pathways downstream of NTN4. NTN4 expression was significantly lower in invasive breast carcinoma compared with adjacent non-malignant tissues. Promoter methylation of NTN4 exhibited different patterns in breast cancer. Low expression of NTN4 was associated with poorer survival. NTN4 was significantly positively related to infiltration of CD8 T cells, macrophages and neutrophils, whereas significantly negatively related to B cells and tumor purity. Association patterns varied with different subtypes. Various associations between NTN4 levels and immune cell surface markers were revealed. Different subtypes of breast cancer carried different genetic alterations. Mechanistically, NTN4 was involved in mediating multiple biological processes including morphogenesis and migration.
神经导向因子家族成员 Netrin-4（NTN4）可促进神经突生长和伸长。本研究旨在探讨 NTN4 是否与乳腺癌的预后和免疫浸润相关。通过公共数据库和组织样本免疫组织化学（IHC）解析 NTN4 在乳腺癌中的预后图谱及其与免疫浸润的关系。使用 UALCAN、TIMER、Kaplan-Meier Plotter 和 Prognoscan 数据库探索 NTN4 的表达谱和预后价值。根据 TIMER，评估 NTN4 表达与肿瘤免疫浸润和免疫细胞表面标志物的关系。使用 cBioPortal 数据库研究 NTN4 在乳腺癌中的转录和生存分析。使用 STRING 数据库探索 NTN4 下游的分子功能和信号通路。与相邻非恶性组织相比，浸润性乳腺癌中 NTN4 的表达显著降低。NTN4 的启动子甲基化在乳腺癌中呈现不同的模式。NTN4 低表达与生存率降低相关。NTN4 与 CD8+T 细胞、巨噬细胞和中性粒细胞浸润呈显著正相关，而与 B 细胞和肿瘤纯度呈显著负相关。与不同的亚型有关。揭示了 NTN4 水平与免疫细胞表面标志物之间的各种关联。不同亚型的乳腺癌具有不同的遗传改变。从机制上讲，NTN4 参与介导多种生物学过程，包括形态发生和迁移。
