Comprehensive Pan-Cancer Analysis of IRAK Family Genes Identifies IRAK1 as a Novel Oncogene in Low-Grade Glioma

BACKGROUND: The interleukin-1 receptor-associated kinases (IRAK) family genes, indispensable mediators of interleukin-1 receptor (IL1R) and Toll-like receptor (TLR)-inflammatory signaling, may be involved in the biological function of human cancers due to the crucial roles of inflammation in tumor development. Though a little research has demonstrated the function of individual IRAK family members in specific tumors, comprehensive analysis is still lacking in pan-cancer. METHODS: We analyzed the mRNA expression landscape, mutation, and prognosis value of IRAK genes based on The Cancer Genome Atlas (TCGA), cBioPortal, GlioVis, and Rembrandt databases. The correlation between the expression of IRAK genes and tumor microenvironment (TME), Stemness score, and immune subtypes was explored. Western blot, cell proliferation, apoptosis, migration assays, and xenograft models were utilized in this study. RESULTS: We found that the expression of IRAK genes extensively changed and was related to patient survival in pan-cancer. Besides, IRAK family genes were correlated with TME, Stemness score, and immune subtypes in most cases. Given that high expression of all IRAK family members predicted poor prognosis in low-grade glioma (LGG), the oncogenic function of the highest expressed IRAK1 in LGG has been confirmed in vitro and in vivo. IRAK1 was uncovered to inhibit cell apoptosis and augment malignancy of LGG in vitro and in vivo. CONCLUSION: These findings revealed the potential targets of IRAK family genes in pan-cancer and provided insights for further investigation of IRAK1 as a novel oncogenic gene in LGG.