Zeng Liang, Liu Xiao-Yun, Miao Lei, Chen Kai, Xu Hui, Qin Liang-Jun, Li Meng, Liu Kai, Feng Jiahao, Wang Hai-Yun
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 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.
iScience. 2023 Jan 13;26(2):105974. doi: 10.1016/j.isci.2023.105974. eCollection 2023 Feb 17.
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.
异常的微小染色体维持蛋白（MCM）表达与肿瘤发生相关。在此，我们进行了免疫组织化学结合数字病理学分析，以确定130例神经母细胞瘤患者中MCM2/5/6的表达情况。使用最小绝对收缩和选择算子建立了一个风险评分，该评分根据MCM2表达、年龄以及治疗应用研究以产生有效治疗方案（TARGET）数据集中的国际神经母细胞瘤分期系统来预测预后（n = 150），其中高危患者的预后明显更差，这在一个基于医院的队列（n = 130）中得到了验证。经过多变量调整后，风险模型在TARGET队列中仍然是生存的独立因素（总生存期[OS]：风险比[HR] 2.3，95%置信区间[CI] 1.4 - 4.0；无事件生存期[EFS]：HR 1.8，95% CI 1.1 - 3.1），在验证队列中对OS也是如此（HR 8.3，95% CI 1.6 - 44.5）。ESTIMATE分析表明，风险模型与低ESTIMATE和基质评分呈负相关。这些发现显示了该评分的累加性质，有助于其未来与新的预后变量一起实施。
