Department of Orthopeadic Surgery, People's Hospital of Dongxihu District, Wuhan, Hubei.
Department of Nuclear Medicine.
Medicine (Baltimore). 2020 Dec 18;99(51):e23772. doi: 10.1097/MD.0000000000023772.
Numerous reports have demonstrated that DNA methylation may be underlying prognostic biomarkers of cancer. However, few studies indicated that DNA methylation was independent biomarker for osteosarcoma prognosis. We aimed to discover and validate a novel DNA methylation signature for prediction of osteosarcoma patients' overall survival (OS).The DNA methylation data of osteosarcoma patients was researched from The Cancer Genome Atlas (TCGA) database. Overall, 80 samples with 485,577 DNA methylation sites were enrolled in our study. The 80 samples were randomly allocated into training dataset (first two-thirds) and validation dataset (remaining one-third). Initially, the univariate Cox proportional hazard analysis was performed in the training dataset to determine methylation sites significantly (P < .05) relevant to osteosarcoma patients' OS as underlying indicators. Subsequently, the underlying indicators were employed to carry out the least absolute shrinkage and selection operator (LASSO) Cox regression analysis for further selecting the candidate methylation sites. Then, the selected candidate methylation sites were employed as covariates to perform multivariate Cox proportional hazard model for identifying the predictor of OS in osteosarcoma patients. The validation dataset was used to validate the predictive accuracy by receiver operating characteristic (ROC) analysis and Kaplan-Meier survival analysis.We discovered a 7-DNA methylation signature closely relevant to OS of osteosarcoma patients. AUC at 1, 3, 5 years in training dataset (0.951, 0.922, 0.925, respectively), testing dataset (0.952, 0.918, 0.925, respectively), and entire dataset (0.952, 0.968, 0.968, respectively). Suggesting high predictive values for OS of osteosarcoma patients. In addition, a methylation-associated nomogram suggested good predictive value and clinical application.We discovered and validated a novel 7-DNA methylation-associated nomogram for predicting OS of osteosarcoma patients.
大量报告表明，DNA 甲基化可能是癌症预后的潜在生物标志物。然而，很少有研究表明 DNA 甲基化是骨肉瘤预后的独立生物标志物。我们旨在发现和验证一种新的 DNA 甲基化特征，用于预测骨肉瘤患者的总生存期（OS）。
从癌症基因组图谱（TCGA）数据库研究了骨肉瘤患者的 DNA 甲基化数据。总体而言，我们的研究纳入了 80 例样本，其中包含 485,577 个 DNA 甲基化位点。这 80 个样本被随机分配到训练数据集（前三分之二）和验证数据集（剩余三分之一）。最初，在训练数据集中进行单变量 Cox 比例风险分析，以确定与骨肉瘤患者 OS 显著相关（P < .05）的甲基化位点作为潜在指标。随后，使用潜在指标进行最小绝对收缩和选择算子（LASSO）Cox 回归分析，以进一步选择候选甲基化位点。然后，选择候选甲基化位点作为协变量，以进行多变量 Cox 比例风险模型，以确定骨肉瘤患者 OS 的预测因子。验证数据集用于通过接收者操作特征（ROC）分析和 Kaplan-Meier 生存分析验证预测准确性。
我们发现了一个与骨肉瘤患者 OS 密切相关的 7-DNA 甲基化特征。在训练数据集（AUC 分别为 0.951、0.922、0.925）、测试数据集（AUC 分别为 0.952、0.918、0.925）和整个数据集（AUC 分别为 0.952、0.968、0.968）中，该特征对 OS 的预测值均较高。这表明该特征对骨肉瘤患者 OS 具有较高的预测价值。此外，一个基于甲基化的列线图提示了该特征具有良好的预测价值和临床应用价值。
我们发现并验证了一种新的 7-DNA 甲基化相关列线图，用于预测骨肉瘤患者的 OS。
