Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Road 6, Nanning, 530021, Guangxi, People's Republic of China.
Sci Rep. 2023 Oct 28;13(1):18489. doi: 10.1038/s41598-023-45626-x.
This study aimed to screen for small nuclear RNAs (snRNAs) associated with the prognosis of acute myeloid leukemia (AML) by using The Cancer Genome Atlas (TCGA) whole-transcriptome sequencing dataset. A total of 130 AML patients from TCGA cohort with complete prognostic information and transcriptome data were enrolled in the current study. Comprehensive survival and functional enrichment analyses were performed to explore the prognostic value and potential biological functions of prognostic snRNAs in AML patients. In the current study, we screened 72 snRNAs that were notably associated with the clinical outcome of AML and developed an expression signature consist of ten snRNAs, that can be accurately applied to assess the overall survival of AML patients. Functional mechanism analysis revealed that this expression signature may be strongly linked to some classical tumor-associated pathways, such as Notch and Wnt pathways, as well as being closely related to B and T cell receptor pathways. Furthermore, we screened six compounds (chicago sky blue 6 B, 5230742, clorsulon, nefopam, nicardipine, and streptomycin) that may serve as targeted therapeutic drugs for AML using connectivity maps. Tumor immunoassays indicated significant differences in the immune microenvironment of the bone marrow tissue between high-risk and low-risk AML patients. Immune infiltration analysis also revealed significant differences in the abundance of multiple immune cells in the bone marrow of the two groups of AML patients groups. In conclusion, our results revealed a novel prognostic expression signature of AML consisting of ten snRNAs, and we conducted a preliminary exploration of its potential biological functions and tumor immunity.
本研究旨在通过使用癌症基因组图谱(TCGA)全转录组测序数据集筛选与急性髓系白血病(AML)预后相关的小核 RNA(snRNA)。本研究共纳入了来自 TCGA 队列的 130 例具有完整预后信息和转录组数据的 AML 患者。进行了全面的生存和功能富集分析,以探讨预后 snRNA 在 AML 患者中的预后价值和潜在生物学功能。在本研究中,我们筛选出 72 个与 AML 临床结局显著相关的 snRNA,并开发了一个由 10 个 snRNA 组成的表达特征,可以准确地用于评估 AML 患者的总生存期。功能机制分析表明,该表达特征可能与一些经典的肿瘤相关途径密切相关,如 Notch 和 Wnt 途径,并且与 B 和 T 细胞受体途径密切相关。此外,我们使用连接图谱筛选出了六种可能作为 AML 靶向治疗药物的化合物(芝加哥天蓝色 6B、5230742、氯舒隆、奈福泮、尼卡地平、链霉素)。肿瘤免疫检测表明,高危和低危 AML 患者骨髓组织的免疫微环境存在显著差异。骨髓中两种 AML 患者组中多种免疫细胞丰度的免疫浸润分析也显示出显著差异。总之,我们的研究结果揭示了一种由十个 snRNA 组成的新型 AML 预后表达特征,并对其潜在的生物学功能和肿瘤免疫进行了初步探索。