Wang Yun, Hu Fang, Li Jin-Yuan, Nie Run-Cong, Chen Si-Liang, Cai Yan-Yu, Shu Ling-Ling, Deng De-Jun, Xu Jing-Bo, Liang Yang
Sate key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
Front Oncol. 2020 Apr 21;10:540. doi: 10.3389/fonc.2020.00540. eCollection 2020.
Acute myelogenous leukemia (AML) is a heterogeneous disease with recurrent gene mutations and variations in disease-associated gene expression, which may be useful for prognostic prediction. RNA matrix and clinical data of AML were downloaded from GEO, TCGA, and TARGET databases. Prognostic metabolic genes were identified by LASSO analysis to establish a metabolic model. Prognostic accuracy of the model was quantified by time-dependent receiver operating characteristic curves and the area under the curve (AUC). Survival analysis was performed by log-rank tests. Enriched pathways in different metabolic risk statuses were evaluated by gene set enrichment analyses (GSEA). We identified nine genes to construct a prognostic model of shorter survival in the high-risk vs. low-risk group. The prognostic model showed good predictive efficacy, with AUCs for 5-year overall survival of 0.78 (0.73-0.83), 0.76 (0.62-0.89), and 0.66 (0.57-0.75) in the training, adult external, and pediatric external cohorts, respectively. Multivariable analysis demonstrated that the metabolic signature had independent prognostic value with hazard ratios of 2.75 (2.06-3.66), 1.89 (1.09-3.29), and 1.96 (1.00-3.84) in the training, adult external, and pediatric external cohorts, respectively. Combining metabolic signatures and classic prognostic factors improved 5-year overall survival prediction compared to the prediction by classic prognostic factors ( < 0.05). GSEA revealed that most pathways were metabolism-related, indicating potential mechanisms. We identified dysregulated metabolic features in AML and constructed a prognostic model to predict the survival of patients with AML.
急性髓系白血病(AML)是一种异质性疾病,存在复发性基因突变以及疾病相关基因表达的差异,这可能有助于预后预测。从基因表达综合数据库(GEO)、癌症基因组图谱(TCGA)和治疗与儿童癌症研究小组(TARGET)数据库下载了AML的RNA矩阵和临床数据。通过套索分析确定预后代谢基因,以建立代谢模型。通过时间依赖性受试者工作特征曲线和曲线下面积(AUC)对模型的预后准确性进行量化。通过对数秩检验进行生存分析。通过基因集富集分析(GSEA)评估不同代谢风险状态下的富集通路。我们确定了9个基因,构建了高风险组与低风险组中生存期较短的预后模型。该预后模型显示出良好的预测效能,在训练队列、成人外部队列和儿童外部队列中,5年总生存率的AUC分别为0.78(0.73 - 0.83)、0.76(0.62 - 0.89)和0.66(0.57 - 0.75)。多变量分析表明,在训练队列、成人外部队列和儿童外部队列中,代谢特征具有独立的预后价值,风险比分别为2.75(2.06 - 3.66)、1.89(1.09 - 3.29)和1.96(1.00 - 3.84)。与经典预后因素预测相比,结合代谢特征和经典预后因素可改善5年总生存率预测(P < 0.05)。GSEA显示大多数通路与代谢相关,表明了潜在机制。我们确定了AML中失调的代谢特征,并构建了一个预后模型来预测AML患者的生存情况。