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A comparative integrated multi-omics analysis identifies CA2 as a novel target for chordoma
Tong Meng1,2, Runzhi Huang3, Jiali Jin2
1Department of Orthopedics, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
Neuro-Oncology
|July 2, 2021
Summary
This study reveals the bone microenvironment
Area of Science:
- Oncology
- Genomics
- Epigenetics
Background:
- Chordoma is a rare, recurrent mesenchymal malignancy with poorly understood tumorigenesis.
- Genetic, epigenetic, and chromatin organization factors are implicated in chordoma development.
- There is a need for novel therapeutic targets in chordoma treatment.
Purpose of the Study:
- To identify novel therapeutic targets for chordoma using integrated multi-omics analysis.
- To investigate the role of the bone microenvironment in chordoma tumorigenesis.
Main Methods:
- Integrated multi-omics analysis including RNA-sequencing (RNA-seq), ATAC-seq, and Hi-C.
- Comparison between chordoma and human nucleus pulposus (HNP) tissues.
- Validation of target gene expression in clinical samples and functional evaluation in cell and animal models.
Main Results:
- The bone microenvironment plays a significant role in chordoma tumorigenesis.
- Carbonic anhydrase II (CA2) and THNSL2 were identified as key genes involved in chordoma.
- CA2 is highly expressed in chordoma and its inhibition (using Dorzolamide HCl) suppressed tumor cell growth and migration.
- Dorzolamide HCl also impacted the bone microenvironment by inhibiting osteoclast differentiation.
Conclusions:
- The bone microenvironment is crucial in chordoma tumorigenesis.
- Carbonic anhydrase II (CA2) is a novel therapeutic target for chordoma.
- Dorzolamide HCl shows promise as a therapeutic option for chordoma.
