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神经元钙传感器 1 的表达水平可预测细胞遗传学正常 AML 的预后。

The expression level of Neuronal Calcium Sensor 1 can predict the prognosis of cytogenetically normal AML.

机构信息

Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, 100191, Beijing, China.

Department of Respiratory Medicine, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.

出版信息

Pharmacogenomics J. 2023 Jul;23(4):89-94. doi: 10.1038/s41397-023-00301-2. Epub 2023 Mar 14.

DOI:10.1038/s41397-023-00301-2
PMID:36918700
Abstract

Acute myeloid leukemia (AML) is malignant clonal expansion of myeloid blasts with high heterogeneity and numerous molecular biomarkers have been found to judge the prognosis in some specific classifications of AML. Furthermore, as for patients with cytogenetically normal acute myeloid leukemia (CN-AML), we need to find more new biomarkers to predict the patients' outcomes. Recently, the expression level of Neuronal Calcium Sensor 1 (NCS1) has been associated with the prognosis of breast cancer and hepatocellular carcinoma, but nothing related has been reported about hematological malignancies. Therefore, we make this study to explore the relationship between the NCS1 expression level and CN-AML. We analyzed the relation between survival and NCS1 RNA expression through 75 CN-AML patients from Cancer Genome Atlas (TCGA) database and 433 CN-AML patients (3 independent datasets) from Gene Expression Omnibus (GEO) database. Additionally, we compared the NCS1 RNA expression between 138 leukemia stem cells positive (LSCs+) samples and 89 leukemia stem cells negative (LSCs-) samples from 78 AML patients from GSE76004 dataset. In our study, CN-AML patients with high expression level of NCS1 have longer EFS or OS. In addition, the NCS1 expression level in leukemia stem cells was low (p = 0.00039). According to these findings, we concluded that the high expression of NCS1 can predict favorable prognosis in CN-AML patients. Furthermore, our work put forward that NCS1 expresses lower in LSCs+, which might be an important mechanism to explain the aggressiveness of AML.

摘要

急性髓系白血病 (AML) 是髓系原始细胞的恶性克隆性扩增,具有高度异质性,许多分子生物标志物已被发现可用于判断某些特定 AML 分类的预后。此外,对于细胞遗传学正常的急性髓系白血病 (CN-AML) 患者,我们需要寻找更多新的生物标志物来预测患者的预后。最近,神经元钙传感器 1 (NCS1) 的表达水平与乳腺癌和肝细胞癌的预后相关,但尚未有关于血液系统恶性肿瘤的相关报道。因此,我们进行了这项研究,以探讨 NCS1 表达水平与 CN-AML 之间的关系。我们通过癌症基因组图谱 (TCGA) 数据库中的 75 例 CN-AML 患者和基因表达综合数据库 (GEO) 数据库中的 433 例 CN-AML 患者 (3 个独立数据集) 分析了生存与 NCS1 RNA 表达之间的关系。此外,我们比较了来自 GSE76004 数据集的 78 例 AML 患者的 138 例白血病干细胞阳性 (LSCs+) 样本和 89 例白血病干细胞阴性 (LSCs-) 样本之间的 NCS1 RNA 表达。在我们的研究中,NCS1 高表达的 CN-AML 患者的 EFS 或 OS 更长。此外,白血病干细胞中的 NCS1 表达水平较低 (p=0.00039)。根据这些发现,我们得出结论,NCS1 的高表达可预测 CN-AML 患者的良好预后。此外,我们的工作还提出,NCS1 在 LSCs+中表达较低,这可能是解释 AML 侵袭性的重要机制。

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