Department of Hematology, the First Hospital of Lanzhou University, Lanzhou, People's Republic of China.
Hematology. 2021 Dec;26(1):284-294. doi: 10.1080/16078454.2021.1889158.
Immunotherapy based on T cells is a new therapy for Acute myeloid leukemia (AML). However, there has not been considerable improvement compared with traditional chemotherapeutics. This study aimed to identify important immune cells, genes, and drugs associated with the immunotherapy of AML.
The gene expression profile and clinical data of patients with AML were downloaded from TCGA database, and the abundance ratio of immune cells was obtained via CIBERSORT. Kaplan-Meier (KM) survival analysis was used to assess the relationship between immune cells and survival time of patients with AML. Differentially expressed genes (DEGs) analysis was conducted to obtained DEGs related to mast cells. Then, protein-protein interaction (PPI) analysis and enrichment analysis were performed to explore the hub genes. Finally, Connectivity Map (CMap) database was utilized to predicts potential drugs that may reverse or induce the mast cell-related gene expression.
Our study showed that mast cell was correlated with survival time of patients with AML, and 135 genes were screened to be related with mast cells. 6 hub genes were identified via PPI network, and 3 potential small molecule drugs were screened to be related to regulating the mast cell-related gene expression via CMap database.
The hub genes and drugs have high research value and clinical application in AML therapy. Our study not only provides gene targets and small molecule drugs for AML immunotherapy concerning mast cells but also provides new ideas for researchers to explore immunotherapy targets of other tumors.
基于 T 细胞的免疫疗法是急性髓系白血病 (AML) 的一种新疗法。然而,与传统化疗相比,并没有显著改善。本研究旨在确定与 AML 的免疫治疗相关的重要免疫细胞、基因和药物。
从 TCGA 数据库下载 AML 患者的基因表达谱和临床数据,并通过 CIBERSORT 获得免疫细胞的丰度比。Kaplan-Meier (KM) 生存分析用于评估免疫细胞与 AML 患者生存时间之间的关系。进行差异表达基因 (DEG) 分析以获得与肥大细胞相关的 DEG。然后,进行蛋白质-蛋白质相互作用 (PPI) 分析和富集分析,以探索关键基因。最后,利用 Connectivity Map (CMap) 数据库预测可能逆转或诱导肥大细胞相关基因表达的潜在药物。
我们的研究表明,肥大细胞与 AML 患者的生存时间相关,筛选出 135 个与肥大细胞相关的基因。通过 PPI 网络鉴定出 6 个关键基因,并通过 CMap 数据库筛选出 3 种可能与调节肥大细胞相关基因表达相关的潜在小分子药物。
这些关键基因和药物在 AML 治疗中具有很高的研究价值和临床应用价值。我们的研究不仅为 AML 免疫治疗中涉及肥大细胞的基因靶点和小分子药物提供了依据,也为研究人员探索其他肿瘤的免疫治疗靶点提供了新的思路。