Department of Gynaecology, Taikang Tongji (Wuhan) Hospital, Wuhan, China.
Department of Emergency, Taikang Tongji (Wuhan) Hospital, Wuhan, China.
Medicine (Baltimore). 2023 Feb 3;102(5):e32766. doi: 10.1097/MD.0000000000032766.
Accumulating studies demonstrated that DNA methylation may be potential prognostic hallmarks of various cancers. However, few studies have focused on the power of DNA methylation for prognostic prediction in patients with stage III to IV ovarian cancer (OC). Therefore, constructing a methylomics-related indicator to predict overall survival (OS) of stage III to IV OC was urgently required. A total of 520 OC patients with 485,577 DNA methylation sites from TCGA database were selected to develop a robust DNA methylation signature. The 520 patients were clustered into a training group (70%, n = 364 samples) and an internal validation group (30%, n = 156). The training group was used for digging a prognostic predictor based on univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) as well as multivariate Cox regression analysis. The internal and external validation group (ICGC OV-AU project) were used for validating the predictive robustness of the predictor based on receiver operating characteristic (ROC) analysis and Kaplan-Meier survival analysis. We identified a 21-DNA methylation signature-based classifier for stage III-IV OC patients' OS. According to ROC analysis in the internal validation, external validation and entire TCGA set, we proved the high power of the 21-DNA methylation signature for predicting OS (area under the curve [AUC] at 1, 3, 5 years in internal validation set (0.782, 0.739, 0.777, respectively), external validation set (0.828, 0.760, 0.741, respectively), entire TCGA set (0.741, 0.748, 0.781, respectively). Besides, a nomogram was developed via methylation risk score as well as a few clinical variables, and the result showed a high ability of the predictive nomogram. In summary, we used integrated bioinformatics approaches to successfully identified a DNA methylation-associated nomogram, which can predict effectively the OS of patients with stage III to IV OC.
越来越多的研究表明，DNA 甲基化可能是各种癌症潜在的预后标志物。然而，很少有研究关注 DNA 甲基化在 III 期至 IV 期卵巢癌（OC）患者中的预后预测能力。因此，迫切需要构建一个基于甲基组学的指标来预测 III 期至 IV 期 OC 的总生存期（OS）。从 TCGA 数据库中选择了 520 名 OC 患者，共 485,577 个 DNA 甲基化位点，用于开发稳健的 DNA 甲基化特征。这 520 名患者被聚类为训练组（70%，n=364 个样本）和内部验证组（30%，n=156 个样本）。训练组用于基于单因素 Cox 比例风险分析、最小绝对值收缩和选择算子（LASSO）以及多因素 Cox 回归分析挖掘预后预测因子。内部和外部验证组（ICGC OV-AU 项目）用于基于接收者操作特征（ROC）分析和 Kaplan-Meier 生存分析验证预测因子的预测稳健性。我们确定了一个基于 21 个 DNA 甲基化特征的分类器，用于预测 III-IV 期 OC 患者的 OS。根据内部验证、外部验证和整个 TCGA 集的 ROC 分析，我们证明了 21 个 DNA 甲基化特征对 OS 预测的高能力（内部验证集的 AUC 在 1、3、5 年分别为 0.782、0.739、0.777，外部验证集分别为 0.828、0.760、0.741，整个 TCGA 集分别为 0.741、0.748、0.781）。此外，通过甲基化风险评分和一些临床变量开发了一个列线图，结果表明该预测列线图具有较高的能力。总之，我们使用综合生物信息学方法成功地鉴定了一个与 DNA 甲基化相关的列线图，它可以有效地预测 III 期至 IV 期 OC 患者的 OS。
