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

Language

English

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

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.

Keywords

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

Published Open-Access

yes

Recommended Citation

Patel, Tajhal D; Grimm, Sandra L; Kanchi, Rupa S; et al., "Identification of an Early Survival Prognostic Gene Signature for Localized Osteosarcoma Patients" (2024). Faculty and Staff Publications. 1935.
https://digitalcommons.library.tmc.edu/baylor_docs/1935