Dataset Information

Expression and prognosis analysis of DNMT family in acute myeloid leukemia.

ABSTRACT: DNA methyltransferases (DNMTs) by regulating DNA methylation play crucial roles in the progression of hematologic malignancies, especially for acute myeloid leukemia (AML). Accumulating investigations have identified the high incidence of DNMT3A mutation in AML, and it is correlated with poor prognosis. Although a few studies have shown the expression of DNMTs and their clinical significance in AML, the results remain to be discussed. Herein, we systemically analyzed the DNMTs expression and their relationship with clinic-pathological features and prognosis in AML patients. DNMTs expression especially for DNMT3A/3B was closely associated with AML among various human cancers. DNMT3A expression was increased in AML patients, whereas DNMT3B expression was decreased. Significant associations between DNMT3A/B expression and clinic-pathological features/gene mutations were observed. Kaplan-Meier analysis showed that DNMT3A expression was associated with better overall survival (OS) and leukemia-free survival (LFS) among whole-cohort AML, and independently affected OS determined by Cox repression multivariate analysis. Notably, patients that received hematopoietic stem cell transplantation (HSCT) showed significantly better OS and LFS in DNMT3A lower-expressed groups, whereas patients in DNMT3A higher-expressed groups did not. By bioinformatics analysis, DNMT3A expression was found to be positively correlated with several leukemia-associated genes/microRNAs, and DNMT3A was identified as direct targets of miR-429 and miR-29b in AML. Collectively, our study demonstrated that DNMT3A/3B showed significant expression differences in AML. DNMT3A expression acted as a potential prognostic biomarker and may guide treatment choice between chemotherapy and HSCT in AML.

SUBMITTER: Zhang TJ

PROVIDER: S-EPMC7425446 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Expression and prognosis analysis of DNMT family in acute myeloid leukemia.

Zhang Ting-Juan TJ Zhang Liu-Chao LC Xu Zi-Jun ZJ Zhou Jing-Dong JD

Aging 20200626 14

DNA methyltransferases (DNMTs) by regulating DNA methylation play crucial roles in the progression of hematologic malignancies, especially for acute myeloid leukemia (AML). Accumulating investigations have identified the high incidence of DNMT3A mutation in AML, and it is correlated with poor prognosis. Although a few studies have shown the expression of DNMTs and their clinical significance in AML, the results remain to be discussed. Herein, we systemically analyzed the ...[more]

PMID: 32597790

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Project description:Background: Tyrosyl phosphorylation is carried out by a group of enzymes known as non-receptor protein tyrosine phosphatases (PTPNs). In the current investigation, it is hoped to shed light on the relationships between the expression patterns of PTPN family members and the prognosis of acute myeloid leukemia (AML). Methods: PTPN expression was examined using GEPIA and GEO databases. To investigate the connection between PTPN expression and survival in AML patients, we downloaded data from the Broad TCGA Firehose and Clinical Proteomic Tumor Analysis (CPTAC) of the Cancer Genome Atlas (TCGA). We used quantitative real-time PCR (qRT-PCR) to confirm that essential genes were performed in clinical samples and cell lines. We then used western blot to verify that the genes expressed in the above databases were positive in normal tissues, AML patient samples, and AML cell lines. Next, we investigated associations between genome-wide expression profiles and PTPN6 expression using the GEO datasets. We investigated the interactive exploration of multidimensional cancer genomics using the cBioPortal datasets. Using the DAVID database, a study of gene ontology enrichment was performed. The protein-protein interaction (PPI) network was created using the STRING portal, and the gene-gene interaction network was performed using GeneMANIA. Results: Data from GEO and GEPIA revealed that most PTPN family members were linked to AML. Patients with leukemia have elevated levels of several PTPN members. All of the AML patients' poor overall survival (OS, p < .05) was significantly linked with higher expression of PTPN1, PTPN6, and PTPN7. Additionally, clinical samples showed that the expression of PTPN 6, PTPN 7, PTPN 13, and PTPN 14 was higher than normal in AML patients (p = .0116, p = .0034, p = .0092, and p = .0057, respectively) and AML cell lines (p = .0004, p = .0035, p = .0357, and p = .0177, respectively). Western blotting results showed that the expression of PTPN6 in AML samples and AML cell lines was significantly higher than that in normal control samples. Conclusion: Differentially expressed PTPN family members were found in AML. The prognosis of patients and PTPN gene expression were shown to be correlated. PTPN6 is one of these members and may be used as an AML diagnostic and prognostic marker.

Dataset Information

Expression and prognosis analysis of DNMT family in acute myeloid leukemia.

Publications

Expression and prognosis analysis of <i>DNMT</i> family in acute myeloid leukemia.

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