Revealing novel subtypes of synovial sarcoma through single cell transcriptomics

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Synovial sarcoma (SyS) is a soft tissue sarcoma defined by the SS18-SSX fusion.
• It presents with slow growth, metastasis, and varied symptoms.
• The SS18-SSX program drives oncogenesis and diverse tumor phenotypes.

Purpose of the Study:

• To explore molecular diversity within synovial sarcoma using single-cell RNA sequencing.
• To identify and characterize distinct molecular subtypes of SyS.
• To complement traditional SyS classification with molecular insights.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was employed.
• Analysis focused on gene expression profiles to identify subtypes.
• Tumor cell phenotypes and signaling pathways were investigated.

Main Results:

• Four molecular subtypes of SyS were identified: NKD2+, HOXD11+, DCN+, and EPCAM+.
• NKD2+ SyS shows increased BMP signaling, immune escape, and chemoresistance.
• HOXD11+ SyS exhibits high oncogenic program expression and immune suppression.
• DCN+ SyS displays mesenchymal differentiation, reduced SS18-SSX expression, and angiogenesis.
• EPCAM+ SyS shows high differentiation and low oncogenic program expression.

Conclusions:

• Single-cell RNA sequencing reveals significant molecular heterogeneity in SyS.
• The identified subtypes possess distinct biological characteristics and potential clinical implications.
• Monophasic mesenchymal SyS may represent at least two distinct molecular subtypes.