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Identification of prognostic genes in the acute myeloid leukemia microenvironment

机译:急性髓细胞白血病微环境中预后基因的鉴定

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摘要

The tumor microenvironment (TME) has a strong influence on the progression, therapeutic response, and clinical outcome of acute myeloid leukemia (AML), one of the most common hematopoietic malignancies in adults. In this study, we identified TME-related genes associated with AML prognosis. Gene expression profiles from AML patients were downloaded from TCGA database, and immune and stromal scores were calculated using the ESTIMATE algorithm. Immune scores were correlated with clinical features such as FAB subtypes and patient’s age. After categorizing AML cases into high and low score groups, an association between several differentially expressed genes (DEGs) and overall survival was identified. Functional enrichment analysis of the DEGs showed that they were primarily enriched in the immune response, inflammatory response, and cytokine activity, and were involved in signaling processes related to hematopoietic cell lineage, B cell receptor, and chemokine pathways. Two significant modules, dominated respectively by CCR5 and ITGAM nodes, were identified from the PPI network, and 20 hub genes were extracted. A total of 112 DEGs correlated with poor overall survival of AML patients, and 11 of those genes were validated in a separate TARGET-AML cohort. By identifying TME-associated genes, our findings may lead to improved prognoses and therapies for AML.
机译:肿瘤微环境(TME)对急性髓细胞性白血病(AML)(成人中最常见的造血系统恶性肿瘤之一)的进展,治疗反应和临床结果具有重要影响。在这项研究中,我们确定了与AML预后相关的TME相关基因。从TCGA数据库下载了来自AML患者的基因表达谱,并使用ESTIMATE算法计算了免疫和基质评分。免疫评分与诸如FAB亚型和患者年龄等临床特征相关。将AML病例分为高分和低分组后,确定了几种差异表达基因(DEG)与总体生存率之间的关联。对DEG的功能富集分析表明,它们主要在免疫反应,炎症反应和细胞因子活性方面富集,并参与与造血细胞谱系,B细胞受体和趋化因子途径有关的信号传导过程。从PPI网络中确定了两个主要模块,分别由CCR5和ITGAM节点控制,并提取了20个中枢基因。总共112个DEG与AML患者的总体生存期差有关,其中11个基因在另一个TARGET-AML队列中得到了验证。通过鉴定与TME相关的基因,我们的发现可能会改善AML的预后和治疗。

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