Pan-Cancer Landscape of Interferon-Induced Protein 35 and Its Tumor-Promoting Role in Breast Cancer.
INTRODUCTION Interferon-induced protein 35 (IFI35) is a critical regulator of virus-induced immune-inflammatory responses; however, its systematic role in cancer, particularly in breast cancer (BRCA), remains unclear. This study aimed to elucidate the pan-cancer expression profile and prognostic value of IFI35 and to elucidate its functional and clinical significance in BRCA. METHODS Public databases, including The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium, were used to analyze IFI35 expression, prognostic value, and its association with the tumor microenvironment. Protein expression in BRCA was validated on tissue microarrays using immunohistochemistry. The function of IFI35 in proliferation, migration, invasion, and apoptosis of BRCA cells was explored through in vitro experiments and nude mouse xenograft models. RESULTS IFI35 expression was significantly upregulated at both messenger RNA and protein levels in multiple cancers, most prominently in BRCA, as well as in glioblastoma multiforme, head and neck squamous cell carcinoma, kidney renal clear cell carcinoma, and liver hepatocellular carcinoma (P < 0.01). Elevated IFI35 expression was correlated with poorer overall survival and progression-free interval in specific cancer types (hazard ratio >1, P < 0.05). IFI35 expression was positively associated with increased infiltration levels of mast cells, neutrophils, eosinophils, CD4+ T cell subtypes, and cancer-associated fibroblasts across multiple cancer types. Our data confirmed that IFI35 was aberrantly overexpressed in BRCA clinical specimens and cell lines. Functional studies demonstrated that IFI35 knockdown effectively suppressed BRCA cell proliferation, migration, and invasion, while promoting apoptosis. In vivo, IFI35 depletion significantly inhibited xenograft tumor growth. CONCLUSIONS Our study revealed that IFI35 contributes to the progression of BRCA and is a potential therapeutic target for BRCA.