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

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

Ying Song  1 , Weilong Zhang  2 , Xue He  3 , Xiaoni Liu  4 , Ping Yang  2 , Jing Wang  2 , Kai Hu  2 , Weiyou Liu  4 , Xiuru Zhang  5 , Hongmei Jing  6 , Xiaoliang Yuan  7
Affiliations

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

Ying Song et al. J Transl Med. .

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.

Keywords: Cytogenetic normal acute myeloid leukemia (CN-AML); LSC; NCALD; Prognostic factor.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
High NCALD expression predicts worse survival of CN-AML. The X axis represents time and the Y axis represents survival probability. A, Kaplan–Meier curves were used for EFS and OS in different NCALD expression groups of CN-AML in the TCGA dataset. The cutoff value for the high and low NCALD groups was 4.74. EFS, P < 0.0001; OS, P = 0.00011; log rank test. B, Kaplan–Meier curves were used for OS in different NCALD expression groups of CN-AML in GSE12417. The cutoff values for the high and low NCALD groups were 8.1794 (left)/5.882 (right). OS, P < 0.0001; log rank test. C, Kaplan–Meier curves were used for OS in different NCALD expression groups in GSE22778. The cutoff values for the high and low NCALD groups were − 1.384 (left)/− 1.095 (right). OS, P < 0.0001; log rank test
Fig. 2
Fig. 2
High NCALD expression predicts worse survival of allo-HSCT or post-chemotherapy AML patients from the TCGA dataset. The X axis represents time (months) and the Y axis represents survival probability. A, Kaplan–Meier curves were used of EFS and OS in different NCALD expression groups after allo-HSCT. The cutoff value for the high and low NCALD groups was 5.30. EFS, P = 0.0051; OS, P = 0.028; log rank test. B, Kaplan–Meier curves were used of EFS and OS in different NCALD expression group after chemotherapy. The cutoff value for the high and low NCALD groups was 4.66. EFS, P = 0.011; OS, P = 0.0056; log rank test
Fig. 3
Fig. 3
ROC curves of survival for NCALD gene expression in TCGA CN-AML patients. The X axis represents false positive (FP) and the Y axis represents true positive (TP). A, ROC curves for NCALD expression and EFS of 75 TCGA CN-AML patients were performed. AUC reached 0.747 (1 year survival, left panel), 0.809 (2 year survival, middle panel) and 0.873 (3 year survival, right panel) respectively. B, ROC curves for NCALD expression and OS of 75 TCGA CN-AML patients were performed. AUC reached 0.711 (1 year survival, left panel), 0.727 (2 year survival, middle panel) and 0.783 (3 year survival, right panel) respectively. The grey shadow of the curves represents 95% confidence interval
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References

    1. Frohling S, Schlenk RF, Kayser S, Morhardt M, Benner A, Dohner K, et al. Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B. Blood. 2006;108(10):3280–3288. doi: 10.1182/blood-2006-04-014324. - DOI - PubMed
    1. Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood. 2000;96(13):4075–4083. - PubMed
    1. Kantarjian H, O’Brien S, Cortes J, Wierda W, Faderl S, Garcia-Manero G, et al. therapeutic advances in leukemia and myelodysplastic syndrome over the past 40 years. Cancer. 2008;113(70):1933–1952. doi: 10.1002/cncr.23655. - DOI - PMC - PubMed
    1. Ravandi F. Relapsed acute myeloid leukemia: why is there no standard of care? Best Pract Res Clin Haematol. 2013;26(3):253–259. doi: 10.1016/j.beha.2013.10.005. - DOI - PMC - PubMed
    1. Kreso A, Dick JE. Evolution of the cancer stem cell model. Cell Stem Cell. 2014;14(3):275–291. doi: 10.1016/j.stem.2014.02.006. - DOI - PubMed

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