NTN4 as a prognostic marker and a hallmark for immune infiltration in breast cancer

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.