Risk model based on minichromosome maintenance 2 using objective assessment for predicting survival of neuroblastoma
Liang Zeng,
Xiao-Yun Liu,
Lei Miao,
Kai Chen,
Hui Xu,
Liang-Jun Qin,
Meng Li,
Kai Liu,
Jiahao Feng,
Hai-Yun Wang
Affiliations
Liang Zeng
Department of Pathology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children’s Medical Center for South Central Region, No. 9 Jinsui Road, Guangzhou 510623, People’s Republic of China; Corresponding author
Xiao-Yun Liu
Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, People’s Republic of China
Lei Miao
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children’s Medical Center for South Central Region, Guangzhou 510623, People’s Republic of China
Kai Chen
Department of Pathology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children’s Medical Center for South Central Region, No. 9 Jinsui Road, Guangzhou 510623, People’s Republic of China
Hui Xu
Department of Pathology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children’s Medical Center for South Central Region, No. 9 Jinsui Road, Guangzhou 510623, People’s Republic of China
Liang-Jun Qin
Department of Pathology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children’s Medical Center for South Central Region, No. 9 Jinsui Road, Guangzhou 510623, People’s Republic of China
Meng Li
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children’s Medical Center for South Central Region, Guangzhou 510623, People’s Republic of China
Kai Liu
Cells Vision (Guangzhou) Medical Technology Inc., Guangzhou 510320, People’s Republic of China
Jiahao Feng
Cells Vision (Guangzhou) Medical Technology Inc., Guangzhou 510320, People’s Republic of China
Hai-Yun Wang
Department of Pathology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children’s Medical Center for South Central Region, No. 9 Jinsui Road, Guangzhou 510623, People’s Republic of China; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangdong Provincial Clinical Research Center for Child Health, National Children’s Medical Center for South Central Region, Guangzhou 510623, People’s Republic of China; Corresponding author
Summary: 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.
