Dataset Information

Serum miR-22 is a novel prognostic marker for acute myeloid leukemia.

ABSTRACT: BACKGROUND:It has been demonstrated that aberrant expression of serum microRNAs is potential markers for the prognostic prediction of acute myeloid leukemia (AML). However, the clinical significance of serum miR-22 remained uncovered. In this study, we aimed to explore the potential prognostic value of serum miR-22 for AML. METHODS:Blood samples were collected from 124 patients with AML and 60 healthy individuals. Serum miR-22 level was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and its potential clinical value was investigated. RESULTS:Our results showed that serum miR-22 expression was significantly downregulated in AML subjects compared to healthy controls. Serum miR-22 levels were lowest in AML patients with M4/M5 subtypes, and low serum miR-22 expression occurred more frequently in AML patients with higher white blood cell counts or poor cytogenetic risk. Receiver operating characteristic (ROC) analysis revealed that serum miR-22 well differentiated AML cases from healthy controls. In addition, serum miR-22 downregulation was closely associated with worse clinical features and shorter survival. Low serum miR-22 expression was confirmed to be an independent predictor for overall survival and relapse-free survival in AML patients. Moreover, the expression level of serum miR-22 was dramatically increased following treatment. In addition, serum miR-22 levels were significantly higher in AML patients achieving complete remission (CR) than those without CR. CONCLUSION:Collectively, serum miR-22 might serve as a novel and promising prognostic biomarker for AML.

SUBMITTER: Qu H

PROVIDER: S-EPMC7521259 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Serum miR-22 is a novel prognostic marker for acute myeloid leukemia.

Qu Hong H Zheng Guodong G Cheng Shuqin S Xie Weicheng W Liu Xiaoshu X Tao Yuan Y Xie Bixia B

Journal of clinical laboratory analysis 20200612 9

<h4>Background</h4>It has been demonstrated that aberrant expression of serum microRNAs is potential markers for the prognostic prediction of acute myeloid leukemia (AML). However, the clinical significance of serum miR-22 remained uncovered. In this study, we aimed to explore the potential prognostic value of serum miR-22 for AML.<h4>Methods</h4>Blood samples were collected from 124 patients with AML and 60 healthy individuals. Serum miR-22 level was detected by quantitative reverse transcripti ...[more]

PMID: 32533562

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Project description:BACKGROUND:Dysregulation of miRNAs that can act as tumor suppressors or oncogenes can result in tumorigenesis. Previously we demonstrated that miR-199b was significantly downregulated in acute myeloid leukemia (AML) and targets podocalyxin and discoidin domain receptor 1. Herein we investigated the functional role of miR-199b in AML and its prognostic implications. METHODS:Major approaches include transduction of hematopoietic stem cells and bone marrow transplantation, analyses of blood lineages, histone deacetylases (HDAC) inhibitors, and molecular and clinical data analyses of AML patients using The Cancer Genome Atlas (TCGA). RESULTS:We first examined the relative miR-199b expression in steady state hematopoiesis and showed CD33(+) myeloid progenitors had the highest miR-199b expression. Further, silencing of miR-199b in CD34(+) cells resulted in significant increases in CFU-GM colonies. Via TCGA we analyzed the molecular and clinical characteristics of 166 AML cases to investigate a prognostic role for miR-199b. The Kaplan-Meier curves for high and low expression values of miR-199b and the observed distribution of miRNA expression revealed the highly expressed group had significantly better survival outcomes (p < 0.016, log rank test). Additionally, there was significant difference between miR-199b expression across the AML subtypes with particularly low expression found in the FAB-M5 subtype. Furthermore, FAB-M5 subtype showed a poor prognosis with a 1-year survival rate of only 25 %, compared with 51 % survival in the overall sample (p < 0.024). Furthermore, significant inverse correlation of HoxA7 and HoxB6 expression with miR-199b was observed in FAB-M5 AML patients. Molecular mutations were analyzed among miR-199b high and low AML cases. Significant correlations in terms of association and survival outcomes were observed for NPMc and IDH1 mutations. Treatment of THP-1 cells (represents M5-subtype) with HDAC inhibitors AR-42, Panobinostat, or Decitabine showed miR-199b expression was significantly elevated upon AR-42 and Panobinostat treatment. To further understand the hematopathological consequences of decreased miR-199b, we employed a bone-marrow transduce/transplant (BMT) mouse model. Interestingly, in vivo miR-199b silencing per-se in HSCs did not result in profound perturbations. CONCLUSIONS:Loss of miR-199b can lead to myeloproliferation while HDAC inhibitors restore miR-199b expression and promote apoptosis. Low miR-199b in AML patients correlates with worse overall survival and has prognostic significance for FAB-M5 subtype.

Project description:BackgroundAcute myeloid leukemia (AML) is a clonal malignant disease with poor prognosis and a low overall survival rate. Although many studies on the treatment and detection of AML have been conducted, the molecular mechanism of AML development and progression has not been fully elucidated. The present study was designed to pursuit the molecular mechanism of AML using a comprehensive bioinformatics analysis, and build an applicable model to predict the survival probability of AML patients in clinical use.MethodsTo simplify the complicated regulatory networks, we performed the gene co-expression and PPI network based on WGCNA and STRING database using modularization design. Two machine learning methods, A least absolute shrinkage and selector operation (LASSO) algorithm and support vector machine-recursive feature elimination (SVM-RFE), were used to filter the common hub genes by five-fold cross-validation. The candidate hub genes were used to build the predictive model of AML by the cox-proportional hazards analysis, and validated in The Cancer Genome Atlas (TCGA) cohort and ohsu cohort, which were reliable in the experimental verification by qRT-PCR and western blotting in mRNA and protein levels.ResultsThree hub genes, FLT3, CD177 and TTPAL were used to build a clinically applicable model to predict the survival probability of AML patients and divided them into high and low groups. To compare the survival ability of the model with the classical clinical features, we generated the nomogram. The model displayed the most risk points contrast to other clinical characteristics, which was compatible with the data of cox multivariate regression.ConclusionThis study reveal the novel molecular mechanism of AML, and construct a clinical model significantly related to AML patient prognosis. We showed the integrated roles of critical pathways, hub genes associated, which provide potential targets and new research ideas for the treatment and early detection of AML.

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Serum miR-22 is a novel prognostic marker for acute myeloid leukemia.

Publications

Serum miR-22 is a novel prognostic marker for acute myeloid leukemia.

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