# 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.

## Key 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.