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A Novel Six Metastasis-Related Prognostic Gene Signature for Patients With Osteosarcoma

Authors :
Yonglong Qiu
Kezhou Xia
Weichun Guo
Wei Li
Changtian Gong
Di Zheng
Ling Yu
Jian Yang
Yubo Shi
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.

Details

ISSN :
2296634X
Volume :
9
Database :
OpenAIRE
Journal :
Frontiers in cell and developmental biology
Accession number :
edsair.doi.dedup.....76cef9aa080c6f7954256c42e0f8f694