Overexpressed MET drives aggressive thyroid cancer phenotypes and serves as a precision therapeutic target

TL;DR

This study shows that overexpression of the MET gene drives aggressive thyroid cancer and suggests targeting MET could improve treatment.

Contribution

The study identifies MET as a precision therapeutic target and molecular classifier for aggressive thyroid cancer.

Findings

The MET gene is significantly overexpressed in thyroid cancer tissues compared to normal controls.

High MET expression is linked to aggressive tumor traits like metastasis and reduced survival.

MET knockdown in thyroid cancer cells reduces migration and invasion in laboratory tests.

Abstract

The global incidence of thyroid carcinoma (THCA) is increasing. Although generally indolent with a favorable prognosis, a subset of cases exhibits aggressive progression. Conventional chemotherapy frequently induces severe systemic toxicity owing to poor target specificity, highlighting the need for more targeted therapeutic approaches. The HGF/c-MET signaling pathway plays a pivotal role in tumorigenesis and disease progression, promoting malignant tumor development through diverse mechanisms, including cell proliferation and migration. By combining integrated multi-omics bioinformatics analysis with functional experiments, this study demonstrates that the MET gene represents a promising theragnostic marker for THCA. Specifically, our study demonstrated: (1) The MET gene is significantly overexpressed in THCA tissues compared to normal controls; (2) This dysregulation is closely associated with aggressive malignant phenotypes, including enhanced tumor progression, increased metastatic potential, reduced survival, and immune-suppressive characteristics; (3) Retrospective clinical case analysis indicated that the lymph node metastasis rate was significantly elevated in the MET high-expression group relative to the low-expression group; (4) RNA interference (RNAi)-mediated MET knockdown resulted in a marked decrease in the migratory and invasive capacities of thyroid cancer cells in vitro. Collectively, these findings not only identify MET as a robust molecular classifier for THCA but, more critically, uncover its therapeutic potential as an actionable target within the HGF/c-MET axis for refractory THCA, providing both experimental evidence and a theoretical framework for developing precision diagnostic and therapeutic strategies.

The online version contains supplementary material available at 10.1038/s41598-025-23587-7.

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