IRF4 as a molecular biomarker in pan-cancer through multiple omics integrative analysis†

IRF4, characterized by its unique helix-turn-helix DNA-binding motif, is a member of the interferon regulatory factor (IRF) family. It plays a critical role in regulating host defense mechanisms, including innate and adaptive immune responses, as well as oncogenesis. However, the precise role of IRF4 in malignant tumors remains poorly understood. In this study, we first investigated IRF4 gene expression across various cancer types and its distribution within different molecular and immunological subtypes, providing a comprehensive understanding of its expression patterns in pan-cancer. We further explored the interacting proteins, diagnostic significance, molecular characteristics, prognostic relevance, and biological functions of IRF4 in diverse cancers. Focusing on colorectal cancer (CRC), we conducted a detailed analysis of IRF4, examining its associations with clinical features and outcomes across multiple clinical subgroups and databases. Additionally, we assessed IRF4 expression at both transcriptional and translational levels in CRC tumor specimens using tissue microarrays. Our findings revealed that IRF4 expression varies significantly not only across cancer types but also among molecular and immunological subtypes. In CRC, elevated IRF4 expression was associated with poorer overall survival. Notably, IRF4 was predominantly expressed in immune cells and showed a strong correlation with tumor immune regulation. Given its high predictive accuracy for cancer outcomes and robust prognostic associations, IRF4 may serve as a valuable prognostic biomarker for CRC. In conclusion, IRF4 represents a unique molecular biomarker for pan-cancer prognosis and an independent prognostic risk factor for CRC. Its critical role in immune regulation also positions IRF4 as a promising target for immunotherapeutic strategies in CRC.