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高 NCALD 表达预示核型正常急性髓系白血病的不良预后。

High NCALD expression predicts poor prognosis of cytogenetic normal acute myeloid leukemia.

机构信息

The First Clinical College of Gannan Medical University, Ganzhou, 341000, China.

Department of Hematology, Lymphoma Research Center, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, People's Republic of China.

出版信息

J Transl Med. 2019 May 20;17(1):166. doi: 10.1186/s12967-019-1904-5.

Abstract

BACKGROUND

Acute myeloid leukemia (AML) is a heterogeneous disease in terms of genetic basis, clinical, biological and prognostic, and is a malignant clonal disease of leukemia stem cells (LSCs). Nearly half of adult AML patients exhibit a cytogenetic normal acute myeloid leukemia (CN-AML). The expression level of NCALD gene was associated with the prognosis of ovarian cancer and non-small cell lung cancer (NSCLC). The expression level of NCALD gene is still unclear in the prognosis of patients with AML.

METHOD

We integrated 5 independent datasets totally 665 AML patients (497 CN-AML patients) to analyzed relation between NCALD gene expression and the clinical FAB classification, gene mutation, therapy, prognosis of CN-AML. We analyzed the NCALD gene expression with the prognosis and LSC of 165 AML patients from The Cancer Genome Atlas (TCGA) dataset and 78 AML patients from GEO dataset.

RESULTS

High NCALD-expressing CN-AML patients were associated with poor event-free survival (EFS) and overall survival (OS) compared to low NCALD expression (EFS, P < 0.0001, OS, P < 0.0001). In AML patients of allogeneic hematopoietic stem cell transplantation (allo-HSCT), high NCALD expression was associated with poor survival prognosis in EFS and OS (EFS, P < 0.0051, OS, P = 0.028). Post-chemotherapy in AML patients, high NCALD expression led a worse prognosis in EFS and OS (EFS, P = 0.011; OS, P = 0.0056). In multivariate analysis, high NCALD expression was an independent prognostic factor that predicts shorter EFS and OS (EFS, P = 3.84E-05, OS, P = 8.53E-05) of CN-AML.

CONCLUSION

Our results indicate that high expression of NCALD gene is a poor prognostic factor for CN-AML. NCALD can be considered as independent predictors of CN-AML patients and can be used as a biomarker for the prognosis of CN-AML.

摘要

背景

急性髓系白血病(AML)在遗传基础、临床、生物学和预后方面存在异质性,是白血病干细胞(LSCs)的恶性克隆性疾病。近一半的成人 AML 患者表现为核型正常的急性髓系白血病(CN-AML)。NCALD 基因的表达水平与卵巢癌和非小细胞肺癌(NSCLC)的预后相关。NCALD 基因在 AML 患者预后中的表达水平尚不清楚。

方法

我们整合了 5 个独立数据集,共 665 例 AML 患者(497 例 CN-AML 患者),分析 NCALD 基因表达与 CN-AML 的临床 FAB 分类、基因突变、治疗、预后的关系。我们分析了来自癌症基因组图谱(TCGA)数据集的 165 例 AML 患者和 GEO 数据集的 78 例 AML 患者的 NCALD 基因表达与预后和 LSC 的关系。

结果

与低 NCALD 表达相比,高 NCALD 表达的 CN-AML 患者的无事件生存(EFS)和总生存(OS)较差(EFS,P<0.0001,OS,P<0.0001)。在异基因造血干细胞移植(allo-HSCT)的 AML 患者中,高 NCALD 表达与 EFS 和 OS 预后不良相关(EFS,P<0.0051,OS,P=0.028)。在 AML 患者化疗后,高 NCALD 表达导致 EFS 和 OS 预后更差(EFS,P=0.011;OS,P=0.0056)。多变量分析表明,高 NCALD 表达是预测 CN-AML 患者 EFS 和 OS 较短的独立预后因素(EFS,P=3.84E-05,OS,P=8.53E-05)。

结论

我们的研究结果表明,NCALD 基因的高表达是 CN-AML 的不良预后因素。NCALD 可作为 CN-AML 患者的独立预测指标,并可作为 CN-AML 预后的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f28/6528257/771c68ce1c1d/12967_2019_1904_Fig1_HTML.jpg

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