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

The Pharmacogenomics Journal volume 23, pages 89–94 (2023)Cite this article

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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.

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Fig. 1: Kaplan–Meier curves of EFS and OS for the expression levels of NCS1 from 75 CN-AML patients in TCGA database.
Fig. 2: Kaplan–Meier curves of OS for the expression levels of NCS1 from 329 CN-AML patients in GEO database.
Fig. 3: The comparison of NCS1 expression in CD34(+ or −)/CD38(+ or −) cell fraction groups and LSCs+/LSCs− groups from 78 AML patients from GSE76004.

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Data openly available in a public repository.

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Acknowledgements

The authors thank datasets GSE12417, GSE22778, GSE71014, GSE76004 from GEO database and dataset from TCGA database.

Funding

This work was funded by National Natural Science Foundation of China (81800195), Key Clinical Projects of Peking University Third Hospital (BYSYZD2019026, BYSYDL2021006), interdisciplinary medicine Seed Fund of Peking University (BMU2018MB004), Natural Science Foundation of Beijing Municipality (7182178 and 7132183), China Health Promotion Foundation (CHPF-zlkysx-001) and Wu Jieping Medical Foundation (320.6750).

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Author notes

  1. These authors contributed equally: Weilong Zhang, Jing Wang, Wei Li.

Authors and Affiliations

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

    Weilong Zhang, Jing Wang, Wei Li, Ping Yang, Mingxia Zhu, Kai Hu, Changjian Yan & Hongmei Jing

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

    Xiaoni Liu

  3. General Practice Medicine, The First People’s Hospital of Huzhou, Huzhou, 313000, China

    Yali Zhao

  4. Department of Pathology, Beijing Tiantan Hospital Affiliated with Capital Medical University, 100050, Beijing, China

    Shaoxiang Li, Gehong Dong, Xue He & Xiuru Zhang

  5. Gannan Medical University, Ganzhou, 341000, China

    Changjian Yan

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Contributions

HJ, XZ, XH and CY conceived the project. WZ, JW and WL analyzed the data. WZ, JW, WL, XL, YZ, PY, MZ, KH, SL, GD, CY, XH, XZ and HJ contributed toward the interpretation of the data. All authors wrote and approved the final manuscript.

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Correspondence to Changjian Yan, Xue He, Xiuru Zhang or Hongmei Jing.

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Zhang, W., Wang, J., Li, W. et al. The expression level of Neuronal Calcium Sensor 1 can predict the prognosis of cytogenetically normal AML. Pharmacogenomics J 23, 89–94 (2023). https://doi.org/10.1038/s41397-023-00301-2

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