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Single-Cell Analysis Clarifies Pathological Heterogeneity in Tenosynovial Giant Cell Tumor and Identifies Biomarkers
Yubin Xie1, Chen Chen1,2, Fei Wu3
1Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 518000, P. R. China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 24, 2025
Summary
Diffuse-type tenosynovial giant cell tumor (D-TGCT) exhibits aggressive behavior due to specific tumor cell interactions. This study identifies key pathways and biomarkers (ROR1, PRKD1) for predicting D-TGCT recurrence.
Area of Science:
- Oncology
- Genomics
- Cell Biology
Background:
- Diffuse-type tenosynovial giant cell tumor (D-TGCT) is more aggressive than localized-type (L-TGCT), leading to poorer patient outcomes.
- Understanding the molecular drivers of D-TGCT's aggressive nature is crucial for developing effective treatments.
Purpose of the Study:
- To elucidate the transcriptional differences between D-TGCT and L-TGCT using single-cell RNA sequencing.
- To identify the cellular mechanisms underlying the aggressive behavior of D-TGCT.
- To discover potential biomarkers for predicting D-TGCT recurrence.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of human D-TGCT and L-TGCT lesions.
- Analysis of tumor cell clusters and their interactions with fibroblasts and macrophages.
- Validation of identified biomarkers (ROR1, PRKD1).
Main Results:
- A unique D-TGCT tumor cell cluster was identified, regulating fibroblast differentiation via COL6A3-(ITGAV+ITGB8) interaction.
- APOE+ fibroblasts activated IL-1B+CCL20+ macrophages through the CXCL12/CXCR4 axis, contributing to local aggression.
- ROR1 and PRKD1 were identified and validated as predictive biomarkers for disease recurrence.
Conclusions:
- This study reveals key mechanisms driving D-TGCT aggression, involving specific tumor cell-fibroblast-macrophage interactions.
- Identified biomarkers ROR1 and PRKD1 offer potential for predicting D-TGCT recurrence.
- Findings provide a theoretical basis and potential therapeutic targets for D-TGCT intervention.

