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鉴定和验证信号识别颗粒 14 作为预测急性髓系白血病患者总生存期的预后生物标志物。

Identification and validation of signal recognition particle 14 as a prognostic biomarker predicting overall survival in patients with acute myeloid leukemia.

机构信息

Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Road 6, Nanning, 530021, Guangxi, People's Republic of China.

出版信息

BMC Med Genomics. 2021 May 13;14(1):127. doi: 10.1186/s12920-021-00975-2.

DOI:10.1186/s12920-021-00975-2
PMID:33985510
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8120815/
Abstract

BACKGROUND

This study aimed to determine and verify the prognostic value and potential functional mechanism of signal recognition particle 14 (SRP14) in acute myeloid leukemia (AML) using a genome-wide expression profile dataset.

METHODS

We obtained an AML genome-wide expression profile dataset and clinical prognostic data from The Cancer Genome Atlas (TCGA) and GSE12417 databases, and explored the prognostic value and functional mechanism of SRP14 in AML using survival analysis and various online tools.

RESULTS

Survival analysis showed that AML patients with high SRP14 expression had poorer overall survival than patients with low SRP14 expression. Time-dependent receiver operating characteristic curves indicated that SRP14 had good accuracy for predicting the prognosis in patients with AML. Genome-wide co-expression analysis suggested that SRP14 may play a role in AML by participating in the regulation of biological processes and signaling pathways, such as cell cycle, cell adhesion, mitogen-activated protein kinase, tumor necrosis factor, T cell receptor, DNA damage response, and nuclear factor-kappa B (NF-κB) signaling. Gene set enrichment analysis indicated that SRP14 was significantly enriched in biological processes and signaling pathways including regulation of hematopoietic progenitor cell differentiation and stem cell differentiation, intrinsic apoptotic signaling pathway by p53 class mediator, interleukin-1, T cell mediated cytotoxicity, and NF-κB-inducing kinase/NF-κB signaling. Using the TCGA AML dataset, we also identified four drugs (phenazone, benzydamine, cinnarizine, antazoline) that may serve as SRP14-targeted drugs in AML.

CONCLUSION

The current results revealed that high SRP14 expression was significantly related to a poor prognosis and may serve as a prognostic biomarker in patients with AML.

摘要

背景

本研究旨在通过全基因组表达谱数据集,确定和验证信号识别粒子 14(SRP14)在急性髓系白血病(AML)中的预后价值和潜在功能机制。

方法

我们从癌症基因组图谱(TCGA)和 GSE12417 数据库中获取了一个 AML 全基因组表达谱数据集和临床预后数据,并通过生存分析和各种在线工具探讨了 SRP14 在 AML 中的预后价值和功能机制。

结果

生存分析显示,SRP14 高表达的 AML 患者总生存期较 SRP14 低表达的患者差。时间依赖性接受者操作特征曲线表明,SRP14 对预测 AML 患者预后具有良好的准确性。全基因组共表达分析表明,SRP14 可能通过参与细胞周期、细胞黏附、丝裂原激活蛋白激酶、肿瘤坏死因子、T 细胞受体、DNA 损伤反应和核因子-κB(NF-κB)信号等生物过程和信号通路的调节,在 AML 中发挥作用。基因集富集分析表明,SRP14 在包括造血祖细胞分化和干细胞分化、p53 类调节剂内在凋亡信号通路、白细胞介素-1、T 细胞介导的细胞毒性和 NF-κB 诱导激酶/NF-κB 信号等生物过程和信号通路中显著富集。使用 TCGA AML 数据集,我们还鉴定了四种可能作为 AML 中 SRP14 靶向药物的药物(苯佐那酯、苯扎氯铵、肉桂嗪、盐酸苯海拉明)。

结论

目前的结果表明,高 SRP14 表达与不良预后显著相关,可能作为 AML 患者的预后生物标志物。

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