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急性髓细胞白血病患者新型小核仁 RNA 预后标志物的综合基因组分析。

Integrative genomic analysis of a novel small nucleolar RNAs prognostic signature in patients with acute myelocytic leukemia.

机构信息

Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.

出版信息

Math Biosci Eng. 2022 Jan 7;19(3):2424-2452. doi: 10.3934/mbe.2022112.

Abstract

This study mainly used The Cancer Genome Atlas (TCGA) RNA sequencing dataset to screen prognostic snoRNAs of acute myeloid leukemia (AML), and used for the construction of prognostic snoRNAs signature for AML. A total of 130 AML patients with RNA sequencing dataset were used for prognostic snoRNAs screenning. SnoRNAs co-expressed genes and differentially expressed genes (DEGs) were used for functional annotation, as well as gene set enrichment analysis (GSEA). Connectivity Map (CMap) also used for potential targeted drugs screening. Through genome-wide screening, we identified 30 snoRNAs that were significantly associated with the prognosis of AML. Then we used the step function to screen a prognostic signature composed of 14 snoRNAs (SNORD72, SNORD38, U3, SNORA73B, SNORD79, SNORA73, SNORD12B, SNORA74, SNORD116-12, SNORA65, SNORA14, snoU13, SNORA75, SNORA31), which can significantly divide AML patients into high- and low-risk groups. Through GSEA, snoRNAs co-expressed genes and DEGs functional enrichment analysis, we screened a large number of potential functional mechanisms of this prognostic signature in AML, such as phosphatidylinositol 3-kinase-Akt, Wnt, epithelial to mesenchymal transition, T cell receptors, NF-kappa B, mTOR and other classic cancer-related signaling pathways. In the subsequent targeted drug screening using CMap, we also identified six drugs that can be used for AML targeted therapy, they were alimemazine, MG-262, fluoxetine, quipazine, naltrexone and oxybenzone. In conclusion, our current study was constructed an AML prognostic signature based on the 14 prognostic snoRNAs, which may serve as a novel prognostic biomarker for AML.

摘要

本研究主要利用癌症基因组图谱(TCGA)RNA 测序数据集筛选急性髓系白血病(AML)的预后 snoRNA,并构建 AML 的预后 snoRNA 特征。使用了总共 130 名具有 RNA 测序数据集的 AML 患者进行预后 snoRNA 筛选。snoRNA 共表达基因和差异表达基因(DEG)用于功能注释和基因集富集分析(GSEA)。连接映射(CMap)也用于潜在的靶向药物筛选。通过全基因组筛选,我们确定了 30 个 snoRNA 与 AML 的预后显著相关。然后我们使用步长函数筛选由 14 个 snoRNA 组成的预后特征(SNORD72、SNORD38、U3、SNORA73B、SNORD79、SNORA73、SNORD12B、SNORA74、SNORD116-12、SNORA65、SNORA14、snoU13、SNORA75、SNORA31),可以将 AML 患者明显分为高风险和低风险组。通过 GSEA、snoRNA 共表达基因和 DEG 功能富集分析,我们筛选出了该预后特征在 AML 中大量潜在的功能机制,如磷脂酰肌醇 3-激酶-Akt、Wnt、上皮间质转化、T 细胞受体、NF-κB、mTOR 等经典的癌症相关信号通路。在随后使用 CMap 进行的靶向药物筛选中,我们还鉴定了六种可用于 AML 靶向治疗的药物,它们是阿利马嗪、MG-262、氟西汀、夸普嗪、纳曲酮和氧苯扎林。总之,我们目前的研究构建了基于 14 个预后 snoRNA 的 AML 预后特征,它可能成为 AML 的一种新的预后生物标志物。

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