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Comprehensive RNA Sequencing Analysis Identifies Network Hub Genes and Biomarkers Differentiating Desmoid-type Fibromatosis From Reactive Fibrosis

  • 0Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea.
Laboratory Investigation; a Journal of Technical Methods and Pathology +

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December 1, 2024

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December 1, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Researchers identified key genes and transcription factors driving desmoid-type fibromatosis (DTF), a condition of persistent fibroblast activation. Novel biomarkers, including TWIST2, show promise for improved DTF diagnosis over current standards.

Area Of Science

  • Molecular biology
  • Oncology
  • Genetics

Background

  • Desmoid-type fibromatosis (DTF) is a benign neoplasm with persistent fibroblast activation.
  • The Wnt/β-catenin pathway is implicated, but specific genetic drivers remain unclear.
  • Distinguishing DTF from reactive fibrosis (RF) is crucial for accurate diagnosis and management.

Purpose Of The Study

  • To identify novel driver genes and molecular pathways underlying persistent fibroblast activation in DTF.
  • To discover potential biomarkers for differentiating DTF from RF.

Main Methods

  • Comparative transcriptome analysis of 29 DTF and 14 RF tissue samples.
  • Weighted gene coexpression network analysis (WGCNA) to identify key gene modules.
  • Identification of driver transcription factors and validation of candidate biomarkers via immunohistochemistry.

Main Results

  • Identified 4267 differentially expressed genes (DEGs) specific to DTF, enriched in embryonic limb morphogenesis and muscle contraction pathways.
  • Discovered a 120-gene DTF-specific module, also found in other fibroproliferative disorders.
  • Identified 7 driver transcription factors (e.g., TWIST2, SALL4) and validated 5 genes (TWIST2, LRRC15, CTHRC1, SHOX2, SALL4) as diagnostic biomarkers, with TWIST2 outperforming β-catenin.

Conclusions

  • The study elucidates novel gene modules and transcription factors critical for sustained fibroblast activation in DTF.
  • Identified TWIST2, LRRC15, CTHRC1, SHOX2, and SALL4 as promising biomarkers for improved DTF diagnosis.
  • Findings offer new insights into DTF pathogenesis and potential for enhanced clinical management.

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