Identification of prognostic genes in the acute myeloid leukemia microenvironment
Identification of prognostic genes in the acute myeloid leukemia microenvironment
复制标题
DOI：
10.18632/aging.102477
复制
发表时间：
2019-11-30
期刊：
影响因子：
5.2
通讯作者：
Fu, Denggang
中科院分区：
文献类型：
--
作者：
Huang, Shaoxin;Zhang, Biyu;Fu, Denggang
肿瘤微环境（TME）对成人最常见的造血系统恶性肿瘤之一急性髓性白血病（AML）的进展、治疗反应和临床结局有很大影响。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AML患者的基因表达谱，并使用ESTIMATE算法计算免疫和基质评分。免疫评分与FAB亚型和患者年龄等临床特征相关。在将AML病例分为高分组和低分组后，确定了几个差异表达基因（DEG）与总生存率之间的关联。DEG的功能富集分析表明，它们主要富集在免疫应答、炎症应答和细胞因子活性中，并且参与与造血细胞谱系、B细胞受体和趋化因子途径相关的信号传导过程。从PPI网络中识别出分别由CCR 5和ITGAM节点支配的两个重要模块，并提取出20个枢纽基因。共有112个DEG与AML患者的总体生存率差相关，其中11个基因在单独的TARGET-AML队列中得到验证。通过鉴定TME相关基因，我们的发现可能会改善AML的治疗和治疗。
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.