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开发和验证用于急性髓细胞白血病的 10 个基因预后签名。

Development and validation of a 10-gene prognostic signature for acute myeloid leukaemia.

机构信息

Department of Hematology and Oncology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, China.

School of Life Sciences, Fudan University, Shanghai, China.

出版信息

J Cell Mol Med. 2020 Apr;24(8):4510-4523. doi: 10.1111/jcmm.15109. Epub 2020 Mar 9.

Abstract

Acute myeloid leukaemia (AML) is the most common type of adult acute leukaemia and has a poor prognosis. Thus, optimal risk stratification is of greatest importance for reasonable choice of treatment and prognostic evaluation. For our study, a total of 1707 samples of AML patients from three public databases were divided into meta-training, meta-testing and validation sets. The meta-training set was used to build risk prediction model, and the other four data sets were employed for validation. By log-rank test and univariate COX regression analysis as well as LASSO-COX, AML patients were divided into high-risk and low-risk groups based on AML risk score (AMLRS) which was constituted by 10 survival-related genes. In meta-training, meta-testing and validation sets, the patient in the low-risk group all had a significantly longer OS (overall survival) than those in the high-risk group (P < .001), and the area under ROC curve (AUC) by time-dependent ROC was 0.5854-0.7905 for 1 year, 0.6652-0.8066 for 3 years and 0.6622-0.8034 for 5 years. Multivariate COX regression analysis indicated that AMLRS was an independent prognostic factor in four data sets. Nomogram combining the AMLRS and two clinical parameters performed well in predicting 1-year, 3-year and 5-year OS. Finally, we created a web-based prognostic model to predict the prognosis of AML patients (https://tcgi.shinyapps.io/amlrs_nomogram/).

摘要

急性髓系白血病(AML)是成人急性白血病中最常见的类型,预后较差。因此,最佳风险分层对于合理选择治疗方法和预后评估至关重要。在我们的研究中,从三个公共数据库中总共收集了 1707 例 AML 患者的样本,将其分为荟萃训练、荟萃测试和验证集。荟萃训练集用于构建风险预测模型,其余四个数据集用于验证。通过对数秩检验、单变量 COX 回归分析以及 LASSO-COX,根据 AML 风险评分(AMLRS)将 AML 患者分为高风险和低风险组,AMLRS 由 10 个与生存相关的基因组成。在荟萃训练、荟萃测试和验证集中,低风险组患者的 OS(总生存期)均明显长于高风险组患者(P<.001),并且时间依赖性 ROC 曲线下的 AUC 分别为 1 年时的 0.5854-0.7905、3 年时的 0.6652-0.8066 和 5 年时的 0.6622-0.8034。多变量 COX 回归分析表明,AMLRS 是四个数据集中的独立预后因素。结合 AMLRS 和两个临床参数的列线图在预测 1 年、3 年和 5 年 OS 方面表现良好。最后,我们创建了一个基于网络的预测模型来预测 AML 患者的预后(https://tcgi.shinyapps.io/amlrs_nomogram/)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0419/7176885/c65fc3e2be28/JCMM-24-4510-g001.jpg

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