Autophagy, a highly conserved cellular protein degradation process, has been involved in acute myeloid leukemia (AML). The present study aims to establish a novel, autophagy-related prognostic signature for prediction of AML prognosis. Differentially expressed autophagy-related genes in AML and healthy samples were screened using GSE1159. Univariate Cox regression analysis was applied to determine survival-associated autophagy-related genes in The Cancer Genome Atlas (TCGA) AML cohort. Lasso regression was performed to develop multiple-gene prognostic signatures. A novel six-gene signature (including CASP3, CHAF1B, KLHL24, OPTN, VEGFA, and VPS37C) DC was established for AML prognosis prediction. The Kaplan–Meier survival analysis revealed that patients in the high-risk score group had poorer overall survival (OS). The receiver operating characteristic (ROC) curve validated its good performance in survival prediction in TCGA AML cohort, and the area under the curve value was 0.817. Moreover, our signature could independently predict OS. A nomogram was constructed, including the six-gene signature and other clinical parameters, and predictive efficiency was confirmed using the ROC curve and calibration curve. Furthermore, gene set enrichment analyses identified several tumor-associated pathways that may contribute to explain the potential molecular mechanisms of our signature. Overall, we developed a new autophagy-associated gene signature and nomogram to predict OS of AML patients, which may help in clinical decision-making for AML treatment.

中文翻译：

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自噬相关特征的系统分析揭示了急性髓系白血病的预后预测因子。

自噬是一种高度保守的细胞蛋白质降解过程，已参与急性髓系白血病 (AML)。本研究旨在建立一种新的、与自噬相关的预后特征，用于预测 AML 预后。使用 GSE1159 筛选 AML 和健康样本中差异表达的自噬相关基因。应用单变量 Cox 回归分析来确定癌症基因组图谱 (TCGA) AML 队列中与生存相关的自噬相关基因。进行套索回归以开发多基因预后特征。一种新颖的6个基因标记（包括CASP3，CHAF1B，KLHL24，OPTN，VEGFA，和VPS37C) DC 被建立用于 AML 预后预测。Kaplan-Meier 生存分析显示，高危评分组患者的总生存期 (OS) 较差。受试者工作特征（ROC）曲线验证了其在TCGA AML队列生存预测中的良好性能，曲线下面积值为0.817。此外，我们的签名可以独立预测 OS。构建列线图，包括六基因特征和其他临床参数，并使用 ROC 曲线和校准曲线确认预测效率。此外，基因集富集分析确定了几种可能有助于解释我们签名的潜在分子机制的肿瘤相关通路。总体而言，我们开发了一种新的自噬相关基因特征和列线图来预测 AML 患者的 OS，