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一种新的铁死亡相关基因特征可预测急性髓系白血病的预后并影响免疫微环境。

A novel ferroptosis-related gene signature can predict prognosis and influence immune microenvironment in acute myeloid leukemia.

机构信息

Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

出版信息

Bosn J Basic Med Sci. 2022 Jul 29;22(4):608-628. doi: 10.17305/bjbms.2021.6274.

Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous hematopoietic malignancy that strongly correlates with poor clinical outcomes. Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death which plays an important role in various human cancers. Nevertheless, the prognostic significance and functions of ferroptosis-related genes (FRGs) in AML have not received sufficient attention. The aim of this article was to evaluate the association between FRGs levels and AML prognosis using publicly available RNA-sequencing datasets. The univariate Cox regression analysis identified 20 FRGs that correlate with patient overall survival. The LASSO Cox regression model was used to construct a prognostic 12-gene risk model using a TCGA cohort, and internal and external validation proved the signature efficient. The 12-FRGs signature was then used to assign patients into high- and low-risk groups, with the former exhibiting markedly reduced overall survival, compared to the low-risk group. ROC curve analysis verified the predictive ability of the risk model. Functional analysis showed that immune status and drug sensitivity differed between the 2 risk groups. In summary, FRGs is a promising candidate biomarker and therapeutic target for AML.

摘要

急性髓系白血病(AML)是一种高度异质性的造血恶性肿瘤,与不良的临床结局密切相关。铁死亡是一种铁依赖性、非凋亡形式的细胞死亡,在各种人类癌症中发挥着重要作用。然而,铁死亡相关基因(FRGs)在 AML 中的预后意义和功能尚未得到充分关注。本文旨在使用公开的 RNA 测序数据集评估 FRGs 水平与 AML 预后之间的关联。单因素 Cox 回归分析确定了 20 个与患者总生存相关的 FRGs。LASSO Cox 回归模型使用 TCGA 队列构建了一个预后 12 基因风险模型,内部和外部验证证明了该特征的有效性。然后,该 12-FRGs 特征用于将患者分为高风险组和低风险组,与低风险组相比,前者的总生存率明显降低。ROC 曲线分析验证了风险模型的预测能力。功能分析表明,两个风险组之间的免疫状态和药物敏感性存在差异。总之,FRGs 是 AML 的一种很有前途的候选生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7693/9392974/b1cbaedea23c/BJBMS-22-608-g001.jpg

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