Table1_DNA Methylation Data-Based Classification and Identification of Prognostic Signature of Children With Wilms Tumor.xlsx

Background: As an epigenetic alteration, DNA methylation plays an important role in early Wilms tumorigenesis and is possibly used as marker to improve the diagnosis and classification of tumor heterogeneity. Methods: Methylation data, RNA-sequencing (RNA-seq) data, and corresponding clinical information were downloaded from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. The prognostic values of DNA methylation subtypes in Wilms tumor were identified. Results: Four prognostic subtypes of Wilms tumor patients were identified by consensus cluster analysis performed on 312 independent prognostic CpG sites. Cluster one showed the best prognosis, whereas Cluster two represented the worst prognosis. Unique CpG sites identified in Cluster one that were not identified in other subtypes were assessed to construct a prognostic signature. The prognostic methylation risk score was closely related to prognosis, and the area under the curve (AUC) was 0.802. Furthermore, the risk score based on prognostic signature was identified as an independent prognostic factor for Wilms tumor in univariate and multivariate Cox regression analyses. Finally, the abundance of B cell infiltration was higher in the low-risk group than in the high-risk group, based on the methylation data. Conclusion: Collectively, we divided Wilms tumor cases into four prognostic subtypes, which could efficiently identify high-risk Wilms tumor patients. Prognostic methylation risk scores that were significantly associated with the adverse clinical outcomes were established, and this prognostic signature was able to predict the prognosis of Wilms tumor in children, which may be useful in guiding clinicians in therapeutic decision-making. Further independent studies are needed to validate and advance this hypothesis.背景：作为一种表观遗传修饰，DNA甲基化在早期肾母细胞瘤（Wilms tumor）发生过程中发挥重要作用，有望作为标志物以提升肿瘤异质性的诊断与分型效能。方法：从生成有效治疗方案的临床应用研究（Therapeutically Applicable Research to Generate Effective Treatments, TARGET）数据库下载甲基化数据、RNA测序（RNA-seq）数据及对应临床信息。本研究鉴定了肾母细胞瘤患者DNA甲基化亚型的预后价值。结果：基于312个独立预后性CpG位点开展一致性聚类分析，我们鉴定出肾母细胞瘤患者的4种预后亚型。1号亚型预后最佳，而2号亚型预后最差。我们针对仅在1号亚型中鉴定到的特异性CpG位点进行分析，以此构建预后特征集。预后甲基化风险评分与患者预后密切相关，其受试者工作特征曲线下面积（AUC）达0.802。此外，通过单因素及多因素Cox回归分析证实，基于该预后特征集的风险评分可作为肾母细胞瘤的独立预后因素。最后，基于甲基化数据分析发现，低风险组的B细胞浸润丰度高于高风险组。结论：综上，我们将肾母细胞瘤病例划分为4种预后亚型，该分型可高效识别高危肾母细胞瘤患者。本研究建立了与不良临床结局显著相关的预后甲基化风险评分，该预后特征集能够预测儿童肾母细胞瘤的预后，可为临床医师制定治疗决策提供参考。未来需开展更多独立研究以验证并推进该假说。