IL1RAP promotes EMT and metastatic phenotypes in papillary thyroid carcinoma and is associated with PI3K/AKT signaling activation.

Although papillary thyroid carcinoma (PTC) usually follows an indolent course, lymph node metastasis and locally advanced disease remain clinically important challenges. This study evaluated interleukin-1 receptor accessory protein (IL1RAP) in PTC using pan-cancer datasets, TCGA/GEO thyroid cancer cohorts, and in vitro validation. IL1RAP was upregulated in PTC tissues and cell lines, and higher IL1RAP expression was associated with advanced pathologic stage, lymph node metastasis, extrathyroidal extension, and unfavorable prognostic indicators. Functional assays showed that IL1RAP overexpression increased PTC cell proliferation, migration, invasion, and EMT-like changes, whereas transient IL1RAP silencing produced the opposite pattern. Bioinformatic enrichment and western blot analyses indicated that these cellular effects were accompanied by increased p-AKT with minimal change in total AKT, suggesting possible involvement of PI3K/AKT-related signaling. To our knowledge, this is the first systematic analysis linking IL1RAP to EMT-associated aggressive behavior in PTC. IL1RAP may represent a candidate biomarker associated with aggressive clinicopathological features, while its diagnostic/prognostic utility and therapeutic potential require further validation.