Chen Yuxiao, Zhu Rui, Chen Min, Guo Wenna, Yang Xin, Xu Xin-Jian, Zhu Liucun
Department of Mathematics, Shanghai University, Shanghai 200444, China.
School of Life Sciences, Shanghai University, Shanghai 200444, China.
J Oncol. 2020 May 15;2020:8106212. doi: 10.1155/2020/8106212. eCollection 2020.
Soft tissue sarcomas (STS) are a highly aggressive and heterogeneous group of malignant mesenchymal tumors. The prognosis of patients with advanced or metastatic STS remains poor, and the main therapy of STS patients combines primary surgery, radiotherapy, and chemotherapy. Aberrant DNA methylation shows close association with the pathogenesis and tumor progression. Therefore, DNA methylation biomarkers might have the potential in accurately predicting the survival of STS patients. In order to identify a prognostic biomarker based on DNA methylation sites, a comprehensive analysis of the DNA methylation profile of STS patients in the Cancer Genome Atlas (TCGA) database was performed. All samples were randomly divided into training and testing datasets. Cox proportional hazards regression analysis was performed to identify a prognostic biomarker that contains three DNA methylation sites. The Kaplan-Meier analysis demonstrated that the 3-DNA methylation biomarker discriminated patients into high-risk and low-risk groups, both in the training and in the testing datasets, and the area under the receiver operating characteristic curve values (AUCs) were 0.844 ( < 0.001, 95% CI: 0.740-0.948) and 0.710 ( = 0.002, 95% CI: 0.595-0.823), respectively. Besides, this biomarker presented superior prognostic performance in STS patients with different age, sex, tissue of origin, therapy, and histologic subtypes. Compared with other prognostic biomarkers, this biomarker tended to be a more precise prognostic factor in STS patients. Moreover, methylation sites in this biomarker might provide a new way for clinicians to make decisions regarding the intervention and assess the effectiveness of an individual therapeutic strategy.
软组织肉瘤(STS)是一组具有高度侵袭性且异质性的恶性间充质肿瘤。晚期或转移性STS患者的预后仍然很差,STS患者的主要治疗方法包括初次手术、放疗和化疗。异常的DNA甲基化与发病机制和肿瘤进展密切相关。因此,DNA甲基化生物标志物可能具有准确预测STS患者生存的潜力。为了基于DNA甲基化位点鉴定一种预后生物标志物,对癌症基因组图谱(TCGA)数据库中STS患者的DNA甲基化谱进行了综合分析。所有样本被随机分为训练数据集和测试数据集。进行Cox比例风险回归分析以鉴定一个包含三个DNA甲基化位点的预后生物标志物。Kaplan-Meier分析表明,在训练数据集和测试数据集中,这种3-DNA甲基化生物标志物均能将患者分为高风险组和低风险组,受试者工作特征曲线下面积(AUC)值分别为0.844(<0.001,95%CI:0.740-0.948)和0.710(=0.002,95%CI:0.595-0.823)。此外,该生物标志物在不同年龄、性别、组织来源、治疗方法和组织学亚型的STS患者中表现出卓越的预后性能。与其他预后生物标志物相比,该生物标志物在STS患者中往往是一个更精确的预后因素。此外,该生物标志物中的甲基化位点可能为临床医生做出干预决策和评估个体治疗策略的有效性提供一种新方法。