Comprehensive pan-cancer characterization of IRAK2 as a potential prognostic biomarker and therapeutic target with validation in hepatocellular carcinoma.

backgroundInflammation plays a critical role in cancer initiation and progression by modulating the tumor microenvironment and immune responses. Interleukin-1 receptor-associated kinase 2 (IRAK2) is a key mediator of the Toll-like receptor and interleukin-1 receptor signaling pathways, its pan-cancer expression patterns, genomic and epigenetic features, immune-related roles, and clinical relevance remain unclear.

methodsThe expression patterns of IRAK2 across multiple cancer types, transcript variants, single-cell distribution, prognostic significance, and biological functions were comprehensively evaluated through analyses of multiple databases and multi-dimensional datasets. Furthermore, the correlations of IRAK2 with the immune microenvironment, epigenetic modifications, and drug sensitivity were investigated. The potential role of IRAK2 in hepatocellular carcinoma was further explored through both in vitro and in vivo experiments.

resultsAberrant expression of IRAK2 was observed in the majority of cancer types, with a relatively high proportion of expression detected in macrophages, and was found to be associated with the prognosis of certain cancers. In most cancer types, IRAK2 expression showed significant correlations with immune cell infiltration, the cancer-immunity cycle, major histocompatibility complex molecules, immune checkpoints, tumor mutational burden, microsatellite instability, RNA modifications (including m1A, m5C, and m6A), and DNA methylation sites. Both in vitro and in vivo experiments demonstrated that knockdown of IRAK2 markedly reduced the proliferative capacity of hepatocellular carcinoma cells.

conclusionThe present study highlights the potential of IRAK2 expression as a novel biomarker for predicting the prognosis and immunotherapeutic response across various human cancers.