Single-cell and spatial transcriptomics identify COL6A3 as a prognostic biomarker in undifferentiated pleomorphic...

Area of Science:

• Oncology
• Genomics
• Dermatopathology

Background:

• Undifferentiated pleomorphic sarcoma (UPS) encompasses a spectrum of soft tissue tumors with variable prognoses.
• Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are distinct dermal neoplasms within this class, posing diagnostic challenges due to overlapping features.
• Accurate differentiation is crucial as AFX and PDS exhibit significantly different clinical outcomes.

Discussion:

• Single-cell and spatial transcriptomics were employed to molecularly characterize AFX and PDS.
• Differential gene expression analysis between AFX and PDS revealed potential prognostic markers.
• The identified genes were validated for their predictive capacity in broader undifferentiated pleomorphic sarcoma cohorts.

Key Insights:

• COL6A3 and BGN emerged as top differential genes between AFX and PDS.
• These genes demonstrated predictive value for overall survival in 17 other cancers.
• COL6A3 and BGN independently predicted overall survival and metastasis-free survival in undifferentiated pleomorphic sarcoma patient cohorts.

Outlook:

• COL6A3 showed the strongest association with overall survival in undifferentiated pleomorphic sarcoma patients.
• COL6A3 outperformed a current sarcoma prognostic gene panel in predicting metastasis.
• These findings highlight novel molecular targets for improved prognostication and therapeutic strategies in soft tissue sarcomas.