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Protein Expression Profiles Corresponding to Histological Changes with Denosumab Treatment in Giant Cell Tumors of

Yoshiyuki Suehara1, Taketo Okubo1, Taisei Kurihara1,2

  • 1Department of Orthopedic Surgery, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Proteomics. Clinical Applications
|July 10, 2019
PubMed
Abstract

Insights

Denosumab treatment for giant cell tumors of bone (GCTB) creates distinct stromal cell (SL) and fibro-osseous (FO) lesions. Proteomic analysis revealed unique protein expression profiles in each lesion, offering insights into denosumab

Area of Science:

  • Oncology
  • Bone Tumors
  • Proteomics

Background:

  • Giant cell tumors of bone (GCTB) are aggressive osteolytic bone tumors.
  • Denosumab is an effective treatment for aggressive and recurrent GCTBs.
  • Post-denosumab GCTB samples exhibit two distinct histological lesions: stromal cell (SL) and fibro-osseous (FO) lesions.

Purpose of the Study:

  • To investigate the differential protein expression between SL-lesions and FO-lesions in denosumab-treated GCTB.
  • To identify proteins and pathways involved in the fibro-osseous reaction induced by denosumab treatment.

Main Methods:

  • Comparative proteomic analysis using isobaric tags for relative and absolute quantification (i-TRAQ).
  • Analysis of 12 paired pre- and post-denosumab treatment GCTB samples.
  • Bioinformatic analysis to identify consistently regulated proteins and canonical pathways.

Main Results:

  • Thirty-two and 59 consistently regulated proteins were identified in SL-lesions and FO-lesions, respectively.
  • Twenty-one proteins in SL-lesions and 48 proteins in FO-lesions showed independent expression.
  • The unfolded protein response was identified as a specific pathway in FO-lesions.

Conclusions:

  • The identified proteins and network analysis provide a deeper understanding of denosumab's effects on GCTB.
  • This research elucidates the molecular mechanisms underlying the histological changes observed after denosumab treatment.
  • Findings may guide future therapeutic strategies for GCTB management.

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