In this JCO Precision Oncology Article Insights episode, Natalie DelRocco summarizes "Prognostic Value of the G2 Expression Signature and MYC Overexpression in Childhood High-Grade Osteosarcoma" by Roelof van Ewijk et al. published on May 29, 2025.

TRANSCRIPT

Natalie Del Rocco: Hello, and welcome to JCO Precision Oncology Article Insights. I'm your host, Natalie DelRocco, and today we will be discussing the original report, "Prognostic Value of the G2 Expression Signature and MYC Overexpression in Childhood High-Grade Osteosarcoma." This original report by van Ewijk et al. describes a study of the association between 2 biomarkers and survival outcomes among patients with high-grade osteosarcoma. Osteosarcoma is a disease where not much progress has been made in risk stratification factors that could potentially help patients target lower-risk therapies, less toxic therapies, or therapies that might be more toxic but could help their high-risk osteosarcoma.

So, it's important to identify risk factors that can help target therapies. The G1/G2 gene expression signature is a prognostic risk score developed by a French osteosarcoma group in 2022. They showed in a cohort of 79 osteosarcoma patients that risk score was associated with poorer event-free survival and overall survival. This considers expression of 15 individual genes. MYC amplification was shown in 2023 by a North American osteosarcoma group to be associated with poor overall survival in a cohort of 92 osteosarcoma patients, and this group validated that finding in a localized cohort in the same publication. 

The goal of this particular original report was to assess the prognostic significance of each of these biomarkers in a population independent to those prior publications and, hence, to serve as an external validation of prior findings and to assess these 2 biomarkers in the same study. The investigators considered MYC amplification, defined as having greater than 7 copies; MYC expression as a continuous rather than the previously categorized variable; and G2 expression defined as a continuous variable; and then G2 expression defined as a dichotomous variable with the cut point at the median, as done in the original paper. 

What the investigators found in their primary multivariable Cox proportional hazards regression model, which controlled for additional clinical risk factors such as age, tumor site, tumor size, is that G2 expression and MYC expression as continuous variables were associated with increased hazard of EFS and OS event. MYC amplification was not found to be prognostic. This is not surprising. When we have continuous variables, we have greater statistical power, we decrease the likelihood that an identified cut point in a previous study does not generalize well to either our genetic assay or our patient population. So, we don't have to worry about finding the optimal cut point in our particular patient sample.

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