Abstract
Aberrant minichromosome maintenance (MCM) expression is associated with tumorigenesis. Here, we performed immunohistochemistry integrated with digital pathology to identify MCM2/5/6 expression in 130 neuroblastoma patients. A risk score was established using least absolute shrinkage and selection operator that predicts outcomes according to MCM2 expression, age, and the International Neuroblastoma Staging System in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset (n = 150), where the patients with high risk had significantly worse prognosis that was validated in a hospital-based cohort (n = 130). After multivariable adjustment, the risk model remained an independent factor for survival in the TARGET cohort (overall survival [OS]: hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.4-4.0; event-free survival [EFS]: HR 1.8, 95% CI 1.1-3.1) and for OS in the validation cohort (HR 8.3, 95% CI 1.6-44.5). The ESTIMATE indicates that the risk model is negatively correlated with low ESTIMATE and stromal scores. These findings show the additive nature of this score, fostering its future implementation with new prognostic variables.