Identification of an early survival prognostic gene signature for localized osteosarcoma patients.
Sci Rep
; 14(1): 7327, 2024 03 27.
Article
in En
| MEDLINE
| ID: mdl-38538763
ABSTRACT
Osteosarcoma is the most prevalent bone tumor in pediatric patients. Neoadjuvant chemotherapy has improved osteosarcoma patient survival, however the 5-year survival rate for localized osteosarcoma is 75% with a 30-50% recurrence rate. We, therefore, sought to identify a prognostic gene signature which could predict poor prognosis in localized osteosarcoma patients. Using the TARGET osteosarcoma transcriptomic dataset, we identified a 13-hub gene signature associated with overall survival and time to death of localized osteosarcoma patients, with the high-risk group showing a 22% and the low-risk group showing 100% overall survival. Furthermore, network analysis identified five modules of co-expressed genes that significantly correlated with survival, and identified 65 pathways enriched across 3 modules, including Hedgehog signaling, which includes 2 of the 13 genes, IHH and GLI1. Subsequently, we demonstrated that GLI antagonists inhibited growth of a recurrent localized PDX-derived cell line with elevated IHH and GLI1 expression, but not a non-relapsed cell line with low pathway activation. Finally, we show that our signature outperforms previously reported signatures in predicting poor prognosis and death within 3 years in patients with localized osteosarcoma.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bone Neoplasms
/
Osteosarcoma
Limits:
Child
/
Humans
Language:
En
Journal:
Sci Rep
/
Sci. rep. (Nat. Publ. Group)
/
Scientific reports (Nature Publishing Group)
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: