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Twofold Expression of Receptor Tyrosine Kinase 2 (ROR2) in Giant Cell Tumors of Bone: Outcome of a Case‒Control Study
Shiva S1, Sandeep Kumar Nema2, Shyam Kumar Tripathi3
1Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India 605006.
Abstract:
Suppression or overexpression of transmembrane proteins of the Wnt family and receptor tyrosine kinases (ROR1 and ROR2) is implicated in the causation of cancer. The objective of this study was to determine the expression of ROR2 in patients with giant cell tumor of bone (GCT) by quantitative PCR (qPCR). In this case‒control study, samples of tumor tissue (patients) and bone from the tumor-free margin (controls) were subjected to qPCR in patients who underwent definitive treatment. The GCTs were classified per radiologic classification and histologic grading. Eleven cases and controls, consisting of six men and five women with a mean age of 33.18 ± 12.35 (20-50) years, were included over the study period of 2 years. The median duration since diagnosis was 12 (IQR 9) months. There was a 2.51-fold change (upregulation of ROR2 expression) in cases compared with controls, which was significant (0.00). There was an increase in the expression of ROR2 with tumor grade. However, these differences were not significant (Campanacci (P 0.05 cases and 0.84 controls), Jaffe (P 0.07 cases and 0.44 controls), or Enneking (0.07 cases and 0.44 controls)). Treatment with bisphosphonates (P = 0.17) or denosumab (P = 0.75) had no significant effect on ROR2 expression. Patients with GCT exhibit more than twofold upregulation of ROR2 expression, confirming its role in causing osteoclast-mediated bone destruction. Therefore, ROR2 may be a target for drug development in the treatment of GCT.
Insights
ROR2 expression is significantly upregulated in giant cell tumors of bone (GCT). This finding suggests ROR2 as a potential therapeutic target for GCT treatment and managing bone destruction.
Area of Science:
- Oncology
- Molecular Biology
- Orthopedic Oncology
Background:
- Transmembrane Wnt family proteins and receptor tyrosine kinases (ROR1, ROR2) are implicated in cancer development.
- Giant cell tumor of bone (GCT) is a primary bone tumor where ROR2's role is not fully understood.
Purpose of the Study:
- To investigate the expression levels of ROR2 in patients diagnosed with GCT.
- To explore the correlation between ROR2 expression and GCT characteristics, including tumor grade and treatment response.
Main Methods:
- A case-control study involving 11 GCT patients and matched controls.
- Quantitative PCR (qPCR) was utilized to measure ROR2 gene expression in tumor tissues and healthy bone margins.
- GCTs were classified using established radiologic and histologic grading systems.
Main Results:
- A significant 2.51-fold upregulation of ROR2 expression was observed in GCT tissues compared to controls (P < 0.001).
- ROR2 expression showed a trend of increase with higher tumor grades, although not statistically significant across different grading systems.
- Neither bisphosphonate nor denosumab treatment significantly affected ROR2 expression levels.
Conclusions:
- Patients with GCT demonstrate a substantial upregulation of ROR2, indicating its potential involvement in osteoclast-mediated bone destruction.
- ROR2 represents a promising molecular target for the development of novel therapeutic strategies for GCT.
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