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

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.