IL1RAP associated with aggressive features in papillary thyroid carcinoma

Interleukin-1 receptor accessory protein, or IL1RAP, was associated with aggressive clinicopathological features and metastatic-like behavior in papillary thyroid carcinoma in a study combining pan-cancer datasets, thyroid cancer cohorts and laboratory experiments. Researchers reported elevated IL1RAP expression in papillary thyroid carcinoma tissues and cell lines. Higher expression was linked to advanced pathological stage, lymph node metastasis, extrathyroidal extension and unfavorable prognostic indicators.

Although papillary thyroid carcinoma usually follows an indolent course, lymph node metastases and locally advanced disease remain clinically important challenges. The research team evaluated IL1RAP using publicly available pan-cancer datasets, TCGA/GEO thyroid cancer cohorts and in vitro validation. Across the analyzed datasets and experimental systems, IL1RAP emerged as a candidate marker associated with more aggressive disease characteristics. These findings describe an association in the analyzed cohorts and do not establish that IL1RAP causes the clinical outcomes observed in patients.

Functional assays provided experimental support for the association. When IL1RAP was overexpressed in papillary thyroid carcinoma cells, the cells showed increased proliferation, migration and invasion, together with epithelial-mesenchymal transition-like changes. Transient silencing of IL1RAP produced the opposite pattern: reduced proliferation, migration and invasion, along with less pronounced EMT-like changes. These experiments connect IL1RAP expression with cellular behaviors associated with metastatic and invasive phenotypes, but they were conducted in cell models rather than in patients. The study therefore provides mechanistic evidence within the tested systems without demonstrating a clinical effect in people with papillary thyroid carcinoma.

Bioinformatic enrichment analysis and western blot measurements suggested that the cellular effects were accompanied by increased phosphorylation of AKT, with minimal change in total AKT. The authors interpreted this pattern as possible involvement of PI3K/AKT-related signaling. The evidence supports an association between IL1RAP expression and AKT phosphorylation in the experimental system, rather than a demonstrated mechanism explaining how IL1RAP produces EMT-like or metastatic phenotypes. The findings were reported in Medical Oncology, volume 43, as article 344, with a publication date of 20 October 2026.

IL1RAP may warrant further investigation as a candidate biomarker associated with aggressive papillary thyroid carcinoma, but its diagnostic, prognostic and therapeutic potential requires additional validation. The reported results do not yet show that measuring IL1RAP can reliably classify tumors or predict outcomes in an independent patient population, nor do they establish that targeting IL1RAP would improve treatment. The study’s central conclusion is limited to the relationship observed among IL1RAP expression, aggressive tumor features, EMT-like and metastatic-associated cell behavior, and AKT activation in the analyzed cohorts and laboratory models.

Subject of Research: IL1RAP expression, aggressive tumor features, EMT-like behavior and PI3K/AKT-related signaling in papillary thyroid carcinoma

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

Article References: Zhao, Y., Shao, Y., Guo, Z., & Guo, M. (2026). IL1RAP promotes EMT and metastatic phenotypes in papillary thyroid carcinoma and is associated with PI3K/AKT signaling activation. Medical Oncology, 43(11), Article 344. https://doi.org/10.1007/s12032-026-03453-w

Image Credits: AI Generated

DOI: 10.1007/s12032-026-03453-w

Keywords: IL1RAP, papillary thyroid carcinoma, cancer metastasis, lymph node metastasis, epithelial-mesenchymal transition, PI3K/AKT signaling, AKT phosphorylation, tumor biomarkers, thyroid cancer, cell invasion, promotes, metastatic