Dataset Information

High expression of miR-25 predicts favorable chemotherapy outcome in patients with acute myeloid leukemia.

ABSTRACT:

Background

Acute myeloid leukemia (AML) pertains to a hematologic malignancy with heterogeneous therapeutic responses. Improvements in risk stratification in AML patients are warranted. MicroRNAs have been associated with the pathogenesis of AML.

Methods

To examine the prognostic value of miR-25, 162 cases with de novo AML were classified into two groups according to different treatment regimens.

Results

In the chemotherapy group, cases with upregulated miR-25 expression showed relatively longer overall survival (OS; P = 0.0086) and event-free survival (EFS; P = 0.019). Multivariable analyses revealed that miR-25 upregulation is an independent predictor for extended OS (HR = 0.556, P = 0.015) and EFS (HR = 0.598, P = 0.03). In addition, allogeneic hematopoietic stem cell transplantation (allo-HSCT) circumvented the poor prognosis that was related to miR-25 downregulation with chemotherapy. The expression level pattern of miR-25 coincided with AML differentiation and proliferation, which included HOXA and HOXB cluster members, as well as the HOX cofactor MEIS1. The MYH9 gene was identified as a direct target of miR-25.

Conclusions

The miR-25 levels are correlated with prognosis in AML independently of other powerful molecular markers. The expression of miR-25 may contribute to the selection of the optimal treatment regimen between chemotherapy and allo-HCST for AML patients.

SUBMITTER: Niu M

PROVIDER: S-EPMC6505210 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

High expression of miR-25 predicts favorable chemotherapy outcome in patients with acute myeloid leukemia.

Niu Mingshan M Feng Yuan Y Zhang Ninghan N Shao Tingting T Zhang Huihui H Wang Rong R Yao Yao Y Yao Ruosi R Wu Qingyun Q Cao Jiang J Liu Xuejiao X Liu Yubo Y Xu Kailin K

Cancer cell international 20190507

<h4>Background</h4>Acute myeloid leukemia (AML) pertains to a hematologic malignancy with heterogeneous therapeutic responses. Improvements in risk stratification in AML patients are warranted. MicroRNAs have been associated with the pathogenesis of AML.<h4>Methods</h4>To examine the prognostic value of miR-25, 162 cases with de novo AML were classified into two groups according to different treatment regimens.<h4>Results</h4>In the chemotherapy group, cases with upregulated miR-25 expression sh ...[more]

PMID: 31080363

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Project description:BackgroundAcute myeloid leukemia (AML) is a heterogeneous disease of the hematopoietic system, for which identification of novel molecular markers is potentially important for clinical prognosis and is an urgent need for treatment optimization.MethodsWe selected C-type lectin domain family 11, member A (CLEC11A) for study via several public databases, comparing expression among a variety of tumors and normal samples as well as different organs and tissues. To investigated the relationship between CLEC11A expression and clinical characteristics, we derived an AML cohort from The Cancer Genome Atlas (TCGA); we also investigated the Bloodspot and HemaExplorer databases. The Kaplan-Meier method and log-rank test were used to evaluate the associations between CLEC11A mRNA expression, as well as DNA methylation, and overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). DNA methylation levels of CLEC11A from our own 28 de novo AML patients were assessed and related to chemotherapeutic outcomes. Bioinformatics analysis of CLEC11A was carried out using public databases.ResultsMultiple public databases revealed that CLEC11A expression was higher in leukemia. The TCGA data revealed that high CLEC11A expression was linked with favorable prognosis (OS p-value = 2e-04; EFS p-value = 6e-04), which was validated in GSE6891 (OS p-value = 0; EFS p-value = 0; RFS p-value = 2e-03). Methylation of CLEC11A was negatively associated with CLEC11A expression, and high CLEC11A methylation level group was linked to poorer prognosis (OS p-value = 1e-02; EFS p-value = 2e-02). Meanwhile, CLEC11A hypermethylation was associated with poor induction remission rate and dismal survival. Bioinformatic analysis also showed that CLEC11A was an up-regulated gene in leukemogenesis.ConclusionCLEC11A may be used as a prognostic biomarker, and could do benefit for AML patients by providing precise treatment indications, and its unique gene pattern should aid in further understanding the heterogeneous AML mechanisms.

Project description:Acute myeloid leukemia (AML) is a devastating blood cancer with high heterogeneity and ill-fated outcome. Despite numerous advances in AML treatment, the prognosis remains poor for a significant proportion of patients. Consequently, it is necessary to accurately and comprehensively identify biomarkers as soon as possible to enhance the efficacy of diagnosis, prognosis and treatment of AML. In this study, we aimed to identify prognostic markers of AML by analyzing the cohorts from TCGA-LAML database and GEO microarray datasets. Interestingly, the transcriptional level of microtubule-associated protein TBCB in AML patients was noticeably increased when compared with normal individuals, and this was verified in two independent cohorts (GSE9476 and GSE13159) and with our AML patients. Furthermore, univariate and multivariate regression analysis revealed that high TBCB expression was an independent poor prognostic factor for AML. GO and GSEA enrichment analysis hinted that immune-related signaling pathways were enriched in up-regulated DEGs between two populations separated by the median expression level of TBCB. By constructing a protein-protein interaction network, we obtained six hub genes, all of which are immune-related molecules, and their expression levels were positively linked to that of TBCB. In addition, the high expression of three hub genes was significantly associated with a poor prognosis in AML. Moreover, we found that the tumor microenvironment in AML with high TBCB expression tended to be infiltrated by NK cells, especially CD56bright NK cells. The transcriptional levels of NK cell inhibitory receptors and their ligands were positively related to that of TBCB, and their high expression levels also predicted poor prognosis in AML. Notably, we found that the down-regulation of TBCB suppressed cell proliferation in AML cell lines by enhancing the apoptosis and cell cycle arrest. Finally, drug sensitivity prediction illustrated that cells with high TBCB expression were more responsive to ATRA and midostaurin but resistant to cytarabine, dasatinib, and imatinib. In conclusion, our findings shed light on the feasibility of TBCB as a potential predictor of poor outcome and to be an alternative target of treatment in AML.

Dataset Information

High expression of miR-25 predicts favorable chemotherapy outcome in patients with acute myeloid leukemia.

Background

Methods

Results

Conclusions

Publications

High expression of miR-25 predicts favorable chemotherapy outcome in patients with acute myeloid leukemia.

Similar Datasets

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