Gene expression and pathway bioinformatics analysis detect a potential predictive value of MAP3K8 in thyroid cancer progression

TL;DR

This study identifies MAP3K8 as a potential biomarker linked to thyroid cancer progression and resistance to BRAF-targeted therapy, revealing a novel mechanism underlying disease advancement and poor prognosis.

Contribution

It demonstrates that MAP3K8 is up-regulated in aggressive thyroid cancers and associated with stem cell-like features and worse outcomes, suggesting its role in disease progression and therapy resistance.

Findings

MAP3K8 is up-regulated in poorly differentiated thyroid carcinomas.

High MAP3K8 expression correlates with stem cell-like phenotype.

MAP3K8 expression is associated with poorer prognosis.

Abstract

Thyroid cancer is the commonest endocrine malignancy. Mutation in the BRAF serine/threonine kinase is the most frequent genetic alteration in thyroid cancer. Target therapy for advanced and poorly differentiated thyroid carcinomas include BRAF pathway inhibitors. Here, we evaluated the role of MAP3K8 expression as a potential driver of resistance to BRAF inhibition in thyroid cancer. By analyzing Gene Expression Omnibus data repository, across all thyroid cancer histotypes, we found that MAP3K8 is up-regulated in poorly differentiated thyroid carcinomas and its expression is related to a stem cell like phenotype and a poorer prognosis and survival. Taken together these data unravel a novel mechanism for thyroid cancer progression and chemo-resistance and confirm previous results obtained in cultured thyroid cancer stem cells