Identification of an Early Survival Prognostic Gene Signature for Localized Osteosarcoma Patients

Authors

Tajhal D Patel
Sandra L Grimm
Rupa S Kanchi
Tanmay Gandhi
Amrit Koirala
Jason T Yustein
Cristian Coarfa

Publication Date

3-27-2024

Journal

Scientific Reports

DOI

10.1038/s41598-024-57527-8

PMID

38538763

PMCID

PMC10973371

PubMedCentral® Posted Date

3-27-2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Child, Prognosis, Zinc Finger Protein GLI1, Hedgehog Proteins, Osteosarcoma, Bone Neoplasms. Bone cancer, Paediatric cancer

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.

Comments

Associated Data