Deng Yajun, Yuan Wenhua, Ren Enhui, Wu Zuolong, Zhang Guangzhi, Xie Qiqi
Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University & Affiliated Cancer Hospital of Qinghai University, Xining, Qinghai 810000, P.R. China.
Department of Orthopedics, Xichang People's Hospital, Xichang, Sichuan 615000, P.R. China.
Genomics. 2021 Jan;113(1 Pt 2):785-794. doi: 10.1016/j.ygeno.2020.10.010. Epub 2020 Oct 15.
Risk stratification using prognostic markers facilitates clinical decision-making in treatment of osteosarcoma (OS). In this study, we performed a comprehensive analysis of DNA methylation and transcriptome data from OS patients to establish an optimal methylated lncRNA signature for determining OS patient prognosis. The original OS datasets were downloaded from the the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. Univariate, Lasso, and machine learning algorithm-iterative Lasso Cox regression analyses were used to establish a methylated lncRNA signature that significantly correlated with OS patient survival. The validity of this signature was verified by the Kaplan-Meier curves, Receiver Operating Characteristic (ROC) curves. We established a four-methylated lncRNA signature that can predict OS patient survival (verified in independent cohort [GSE39055]). Kaplan-Meier analysis showed that the signature can distinguish between the survival of high- and low-risk patients. ROC analysis corroborated this finding and revealed that the signature had higher prediction accuracy than known biomarkers. Kaplan-Meier analysis of the clinical subgroup showed that the signature's prognostic ability was independent of clinicopathological factors. The four-methylated lncRNA signature is an independent prognostic biomarker of OS.
使用预后标志物进行风险分层有助于骨肉瘤(OS)治疗中的临床决策。在本研究中,我们对骨肉瘤患者的DNA甲基化和转录组数据进行了全面分析,以建立一个用于确定骨肉瘤患者预后的最佳甲基化长链非编码RNA(lncRNA)特征。原始的骨肉瘤数据集从治疗应用研究以生成有效治疗方法(TARGET)数据库下载。使用单变量、套索和机器学习算法迭代套索Cox回归分析来建立与骨肉瘤患者生存显著相关的甲基化lncRNA特征。通过Kaplan-Meier曲线、受试者工作特征(ROC)曲线验证了该特征的有效性。我们建立了一个可以预测骨肉瘤患者生存的四甲基化lncRNA特征(在独立队列[GSE39055]中验证)。Kaplan-Meier分析表明,该特征可以区分高风险和低风险患者的生存情况。ROC分析证实了这一发现,并表明该特征比已知生物标志物具有更高的预测准确性。临床亚组的Kaplan-Meier分析表明,该特征的预后能力独立于临床病理因素。四甲基化lncRNA特征是骨肉瘤的独立预后生物标志物。