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与 NET 相关的基因特征可预测 AML 预后。

NET-related gene signature for predicting AML prognosis.

机构信息

Department of Hematology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China.

Center of Hematology Research, Anhui Medical University, Hefei, 230601, Anhui, China.

出版信息

Sci Rep. 2024 Apr 20;14(1):9115. doi: 10.1038/s41598-024-59464-y.

DOI:10.1038/s41598-024-59464-y
PMID:38643300
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11032381/
Abstract

Acute Myeloid Leukemia (AML) is a malignant blood cancer with a high mortality rate. Neutrophil extracellular traps (NETs) influence various tumor outcomes. However, NET-related genes (NRGs) in AML had not yet received much attention. This study focuses on the role of NRGs in AML and their interaction with the immunological microenvironment. The gene expression and clinical data of patients with AML were downloaded from the TCGA-LAML and GEO cohorts. We identified 148 NRGs through the published article. Univariate Cox regression was used to analyze the association of NRGs with overall survival (OS). The least absolute shrinkage and selection operator were utilized to assess the predictive efficacy of NRGs. Kaplan-Meier plots visualized survival estimates. ROC curves assessed the prognostic value of NRG-based features. A nomogram, integrating clinical information and prognostic scores of patients, was constructed using multivariate logistic regression and Cox proportional hazards regression models. Twenty-seven NRGs were found to significantly impact patient OS. Six NRGs-CFTR, ENO1, PARVB, DDIT4, MPO, LDLR-were notable for their strong predictive ability regarding patient survival. The ROC values for 1-, 3-, and 5-year survival rates were 0.794, 0.781, and 0.911, respectively. In the training set (TCGA-LAML), patients in the high NRG risk group showed a poorer prognosis (p < 0.001), which was validated in two external datasets (GSE71014 and GSE106291). The 6-NRG signature and corresponding nomograms exhibit superior predictive accuracy, offering insights for pre-immune response evaluation and guiding future immuno-oncology treatments and drug selection for AML patients.

摘要

急性髓系白血病(AML)是一种死亡率较高的恶性血液病。中性粒细胞胞外诱捕网(NETs)影响各种肿瘤结局。然而,AML 中的 NET 相关基因(NRGs)尚未受到太多关注。本研究关注 NRGs 在 AML 中的作用及其与免疫微环境的相互作用。从 TCGA-LAML 和 GEO 队列中下载 AML 患者的基因表达和临床数据。我们通过已发表的文章确定了 148 个 NRGs。使用单变量 Cox 回归分析 NRGs 与总生存期(OS)的相关性。使用最小绝对收缩和选择算子评估 NRGs 的预测效力。Kaplan-Meier 图可视化生存估计。ROC 曲线评估基于 NRG 的特征的预后价值。使用多变量逻辑回归和 Cox 比例风险回归模型构建了一个整合患者临床信息和预后评分的列线图。发现 27 个 NRGs 对患者 OS 有显著影响。CFTR、ENO1、PARVB、DDIT4、MPO 和 LDLR 这 6 个 NRGs 因其对患者生存的强烈预测能力而引人注目。1 年、3 年和 5 年生存率的 ROC 值分别为 0.794、0.781 和 0.911。在训练集(TCGA-LAML)中,高 NRG 风险组的患者预后较差(p<0.001),在两个外部数据集(GSE71014 和 GSE106291)中得到验证。6-NRG 特征和相应的列线图表现出优异的预测准确性,为免疫前反应评估提供了见解,并为 AML 患者的未来免疫肿瘤治疗和药物选择提供了指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/09c36ed95e04/41598_2024_59464_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/4781fc2eb4ae/41598_2024_59464_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/714bf9536fcb/41598_2024_59464_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/c7c693ce2704/41598_2024_59464_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/60dd99778785/41598_2024_59464_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/089b0d48fb2a/41598_2024_59464_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/b7facdedaaea/41598_2024_59464_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/4ed83c2c3b33/41598_2024_59464_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/09c36ed95e04/41598_2024_59464_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/4781fc2eb4ae/41598_2024_59464_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/714bf9536fcb/41598_2024_59464_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/c7c693ce2704/41598_2024_59464_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/60dd99778785/41598_2024_59464_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/089b0d48fb2a/41598_2024_59464_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/b7facdedaaea/41598_2024_59464_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/4ed83c2c3b33/41598_2024_59464_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e67c/11032381/09c36ed95e04/41598_2024_59464_Fig8_HTML.jpg

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