Background: The interferon-inducible transmembrane (IFITM) proteins are localized in the endolysosomal and plasma membranes, conferring cellular immunity to various infections. However, the relationship with carcinogenesis remains poorly elucidated. In the present study, we investigated the role of IFITM in kidney renal clear cell carcinoma (KIRC).
Methods: We utilized the online databases of Oncomine, UALCAN and Human Protein Atlas to analyze the expression of IFITMs and validate their levels in human KIRC cells by qPCR and western blot. Furthermore, we evaluated prognostic significance with the Gene Expression Profiling Interactive Analysis tool (Kaplan-Meier (KM) Plotter) and delineated the immune cell infiltration profile related to IFITMs with the TIMER2.0 database.
Results: IFITMs were overexpressed in KIRC and varied in subtypes and tumor grades. High expression of IFITMs indicated a poor prognosis and more immune cell infiltration, especially endothelial cells and cancer-associated fibroblasts. IFITMs were associated with immune genes, which correlated with poor prognosis of renal clear cell carcinoma. We also explored the enriched network of IFITMs co-occurrence genes and their targeted transcription factors and miRNA. The expression of IFITMs correlated with hub mutated genes of KIRC.
Conclusions: IFITMs play a crucial role in the oncogenesis of KIRC and could be a potential surrogate marker for treatment response to targeted therapies.
Keywords: Interferon-induced transmembrane proteins (IFITM); kidney renal clear cell carcinoma (KIRC); prognosis; tumor infiltration.
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