# Core Epithelial‐to‐Mesenchymal Transition Gene Signature Predicts Metastasis and Poor Survival in Synovial Sarcoma

## TL;DR

This study shows that mesenchymal gene expression in synovial sarcoma tumors is linked to metastasis and worse survival outcomes.

## Contribution

The study identifies a core EMT gene signature as a potential prognostic biomarker for metastasis in synovial sarcoma.

## Key findings

- Metastatic synovial sarcoma tumors show significant enrichment of EMT-related genes.
- Higher EMT scores correlate with worse overall survival in patients.
- EMT status in primary tumors may help guide treatment and surveillance strategies.

## Abstract

Synovial sarcoma (SS) is a rare soft tissue malignancy comprising 5%–10% of all sarcomas, typically affecting young adults. It is characterized by a pathognomonic SS18–SSX gene fusion, with variable histologic subtypes demonstrating epithelial and mesenchymal features. This study investigates the association between epithelial‐to‐mesenchymal transition (EMT) gene expression and metastatic potential in SS.

A retrospective, single‐institution analysis was conducted using primary tumor specimens from 21 treatment‐naïve SS patients. RNA sequencing was performed on formalin‐fixed paraffin‐embedded (FFPE) tissue to assess gene expression profiles. EMT scores were calculated using three independent methods: Hallmark EMT gene set from GSEA, the 76‐gene EMT signature (76GS), and Kolmogorov–Smirnov (KS) testing. Patients were categorized into metastatic and nonmetastatic cohorts, and phenotype‐specific survival analyses were conducted.

Tumors from patients who developed metastases showed significant enrichment of EMT‐related genes (GSEA NES 1.71, P = 0.025), oxidative phosphorylation, and immune‐related pathways. EMT scores were consistently higher (more mesenchymal) in metastatic tumors across all scoring methods. Mesenchymal phenotype was associated with significantly worse overall survival (GSEA log‐rank P = 0.0009).

This study demonstrates a correlation between mesenchymal gene expression signatures and increased metastatic risk in SS. EMT status, derived from primary tumor profiling at diagnosis, may serve as a potential prognostic biomarker. These findings support further investigation into EMT as a stratification tool for tailoring treatment intensity and surveillance strategies in SS.