Bioinformatics analysis of IFI6 as a novel prognostic biomarker and its correlation with immune infiltration in breast cancer

Abstract

Abstract The aim of this study was to identify biomarkers associated with breast cancer prognosis and to explore the underlying pathogenic mechanisms. Interferon alpha-inducible protein 6 (IFI6), known as a proliferative and anti-apoptotic factor, has been implicated in various malignant diseases. However, its biological roles in breast cancer remain poorly understood. To address this, we employed bioinformatics analyses to investigate the expression and prognostic significance of IFI6 in breast cancer. Our findings revealed that IFI6 was upregulated in breast cancer and was associated with histological subtypes and lymph node metastasis status. Kaplan-Meier plotter analysis demonstrated that high IFI6 expression correlated with poor prognosis in breast cancer patients with ER-positive, PR-positive, HER2-positive, and lymph node-positive subtypes. To further enhance clinical applicability, we constructed a prognostic nomogram incorporating IFI6 expression and clinicopathological factors, which showed favorable predictive performance for overall survival. Additionally, IFI6 expression showed significant correlations with infiltrating immune cells, including regulatory T cells (Tregs), M1 macrophages, naïve B cells, and plasma cells. Single-cell RNA sequencing analysis revealed that IFI6 was predominantly expressed in epithelial tumor cells and was associated with altered immune cell composition, suggesting the potential role in shaping the immune microenvironment. Moreover, IFI6 expression was closely associated with several immunomodulators. In conclusion, IFI6 serves as a potential biomarker for immune infiltration and poor prognosis in breast cancer and may offer novel insights into risk stratification and immunotherapeutic strategies.