IFI44 Promotes Clear Cell Renal Cell Carcinoma Progression via PRDX1 and Predicts Poor Prognosis

Clear cell renal cell carcinoma (ccRCC) is a lethal urologic malignancy with limited biomarkers for prognosis and therapeutic stratification. Interferon-induced protein 44 (IFI44) has been implicated in immune regulation, but its role in ccRCC is unclear. To address this gap, we comprehensively investigated the clinical significance, biological roles, and molecular mechanisms of IFI44 in ccRCC pathogenesis. Using integrative transcriptomic analysis of the Gene Expression Omnibus and the Cancer Genome Atlas-Kidney Clear Cell Carcinoma cohorts, we first identified IFI44 as a key candidate gene. Bioinformatic enrichment analyses and immune infiltration profiling were conducted to investigate potential mechanisms. In parallel, we established ccRCC cell lines with stable IFI44 knockdown and evaluated phenotypic changes using Cell Counting Kit-8, Transwell assays, wound-healing assays, and flow cytometry, thereby examining cell proliferation, apoptosis, migration, and invasion. We observed that IFI44 was markedly elevated in ccRCC tissues, and its increased level was closely associated with advanced tumor stage and poorer patient survival. Enrichment analyses indicated that IFI44 participates in pathways related to viral response, RNA splicing, and mRNA processing. Moreover, elevated IFI44 expression may be associated with an immunosuppressive tumor microenvironment, as suggested by increased infiltration of effector T cells and M1 macrophages, along with decreased infiltration of activated dendritic cells. In mechanistic studies, IFI44 knockdown markedly suppressed cell proliferation, triggered apoptosis, and reduced both migratory and invasive capacities, whereas PRDX1 overexpression rescued these phenotypes and PRDX1 was shown to interact with IFI44. In summary, the data show that IFI44 acts as an oncogene in ccRCC, promoting tumor progression through its interaction with PRDX1 while also shaping an immunosuppressive microenvironment, and suggest that IFI44 is a promising biomarker of prognosis and candidate therapeutic target for ccRCC.