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A Novel Six Metastasis-Related Prognostic Gene Signature for Patients With Osteosarcoma
- Source :
- Frontiers in Cell and Developmental Biology, Frontiers in Cell and Developmental Biology, Vol 9 (2021)
- Publication Year :
- 2021
-
Abstract
- Osteosarcoma is the most common malignant bone tumor, and although there has been significant progress in its management, metastases often herald incurable disease. Here we defined genes differentially expressed between primary and metastatic osteosarcoma as metastasis-related genes (MRGs) and used them to construct a novel six-MRG prognostic signature for overall survival of patients with osteosarcoma. Validation in internal and external datasets confirmed satisfactory accuracy and generalizability of the prognostic model, and a nomogram based on the signature and clinical variables was constructed to aid clinical decision-making. Of the six MRGs,FHITis a well-documented tumor suppressor gene that is poorly defined in osteosarcoma. Consistent with tumor suppressor function, FHIT was downregulated in osteosarcoma cells and human osteosarcoma samples. FHIT overexpression inhibited osteosarcoma proliferation, migration, and invasion bothin vitroandin vivo. Mechanistically, FHIT overexpression upregulate the epithelial marker E-cadherin while repressing the mesenchymal markers N-cadherin and vimentin. Our six-MRG signature represents a novel and clinically useful prognostic biomarker for patients with osteosarcoma, and FHIT might represent a therapeutic target by reversing epithelial to mesenchymal transition.
- Subjects :
- 0301 basic medicine
musculoskeletal diseases
Tumor suppressor gene
QH301-705.5
FHIT
Vimentin
Metastasis
03 medical and health sciences
Cell and Developmental Biology
0302 clinical medicine
osteosarcoma
Medicine
metastasis
prognostic model
Epithelial–mesenchymal transition
Biology (General)
neoplasms
Original Research
biology
business.industry
Mesenchymal stem cell
epithelial to mesenchymal transition
Cell Biology
Gene signature
medicine.disease
030104 developmental biology
030220 oncology & carcinogenesis
Cancer research
biology.protein
Osteosarcoma
business
Developmental Biology
Subjects
Details
- ISSN :
- 2296634X
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Frontiers in cell and developmental biology
- Accession number :
- edsair.doi.dedup.....76cef9aa080c6f7954256c42e0f8f694