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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?

SUBMITTER: Song Y

PROVIDER: S-EPMC6528257 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Song Ying Y Zhang Weilong W He Xue X Liu Xiaoni X Yang Ping P Wang Jing J Hu Kai K Liu Weiyou W Zhang Xiuru X Jing Hongmei H Yuan Xiaoliang X

Journal of translational medicine 20190520 1

<h4>Background</h4>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 p ...[more]

PMID: 31109331

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Project description:Secreted frizzled-related proteins (SFRPs) as Wnt signaling antagonists have been found to be dysregulated by promoter hypermethylation in several cancers including acute myeloid leukemia (AML). This study aimed to investigate the methylated status of SFRPs promoter region and its clinical relevance in Chinese non-M3 AML patients.SFRPs methylation in 139 primary non-M3 AML patients was determined using methylation-specific real-time quantitative polymerase chain reaction.The frequency of aberrant methylation was as follows: 30.2% for SFRP1, 27.3% for SFRP2, 5.0% for SFRP4, and 1.4% for SFRP5. Hypermethylation of at least one SFRP gene occurred in 51.8% (72/139) of non-M3 AML patient samples, which was significantly higher compared to normal control (0/21) (P<0.001). Hypermethylation of SFRP1 was potentially associated with N/K-RAS mutations (P=0.043), and the frequency of SFRPs methylation was higher in patients ≥50 years compared to those <50 years, especially for SFRP2 (P<0.05). Furthermore, both whole cohort and cytogenetically normal (CN) patients with high SFRPs-methylated group showed a shorter overall survival (OS) compared to those with low group (P=0.036 and P=0.035, respectively). Moreover, Cox regression multivariate analysis revealed that SFRPs hypermethylation acts as an independent prognostic biomarker among both whole cohort (hazard ratio =1.804, P=0.026) and CN (hazard ratio =2.477, P=0.023) patients. In leukemic cell line HL60 treated with 5-aza-2'-deoxycytidine, the alteration of SFRP1/2 expression inversely correlated with change in SFRP1/2 methylation (r=-0.975, P=0.005 and r=-0.975, P=0.005, respectively). A tendency of negative correlation was observed between SFRP1 expression and its promoter methylation in AML patients (r=-0.334, P=0.038).These findings suggested that hypermethylation of SFRP1/2 was a frequent event and silenced SFRP1/2 expression in AML. Moreover, hypermethylation of SFRPs promoter was an adverse risk factor for OS in Chinese non-M3 AML patients.

Dataset Information

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

Publications

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

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