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Prognostic impact of peripheral blood WT1-mRNA expression in patients with MDS.

ABSTRACT: Few reports suggested a prognostic impact of Wilms'Tumor-1 (WT1)-mRNA overexpression in MDS, but translation into clinical routine was hampered by limited patients numbers, differing sample sources, non-standardized methods/cut-offs. To evaluate whether WT1-mRNA expression yields additional prognostic information, we measured peripheral blood (PB) WT1-mRNA expression in 94 MDS using a standardized assay offering a validated cut-off to discriminate between normal and WT1-mRNA overexpression. Overall, 54 patients (57%) showed WT1-mRNA overexpression, while 40 patients (43%) had normal WT1-mRNA expression. This enabled discrimination between MDS and both healthy controls and non-MDS cytopenias. Furthermore, WT1-mRNA expression correlated with WHO 2016 subcategories and IPSS-R as indicated by mean WT1-mRNA expression and frequency of WT1-mRNA overexpressing patients within respective subgroups. Regarding the entire group, PB WT1-mRNA expression was associated with prognosis, as those patients showing WT1-mRNA overexpression had higher risk for disease progression and AML transformation and accordingly shorter progression-free, leukemia-free and overall survival in univariate analysis. In multivariate analysis, prognostic impact of PB WT1-mRNA expression status was independent of IPSS-R and enabled more precise prediction of PFS, but not OS, within IPSS-R very low/low and intermediate risk groups. Overall, measuring PB WT1-mRNA appears valuable to support diagnostics and refine prognostication provided by the IPSS-R.

SUBMITTER: Rautenberg C

PROVIDER: S-EPMC6851368 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Prognostic impact of peripheral blood WT1-mRNA expression in patients with MDS.

Rautenberg Christina C Germing Ulrich U Pechtel Sabrina S Lamers Marius M Fischermanns Carolin C Jäger Paul P Geyh Stefanie S Haas Rainer R Kobbe Guido G Schroeder Thomas T

Blood cancer journal 20191112 11

Few reports suggested a prognostic impact of Wilms'Tumor-1 (WT1)-mRNA overexpression in MDS, but translation into clinical routine was hampered by limited patients numbers, differing sample sources, non-standardized methods/cut-offs. To evaluate whether WT1-mRNA expression yields additional prognostic information, we measured peripheral blood (PB) WT1-mRNA expression in 94 MDS using a standardized assay offering a validated cut-off to discriminate between normal and WT1-mRNA overexpression. Over ...[more]

PMID: 31719523

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Project description:BACKGROUND:MicroRNAs (miRNAs) are small RNAs regulating gene expression post-transcriptionally. While acquired changes of miRNA and mRNA profiles in cancer have been extensively studied, little is known about expression changes of circulating miRNAs and messenger RNAs (mRNA) in monogenic constitutional anomalies affecting several organ systems, like Marfan syndrome (MFS). We performed integrated miRNA and mRNA expression profiling in blood samples of Marfan patients in order to investigate deregulated miRNA and mRNA networks in these patients which could serve as potential diagnostic and prognostic tools for MFS therapy. METHODS:MiRNA and mRNA expression profiles were determined in blood samples from MFS patients (n = 7) and from healthy volunteer controls (n = 7) by microarray analysis. Enrichment analyses of altered mRNA expression were identified using bioinformatic tools. RESULTS:A total of 28 miRNAs and 32 mRNAs were found to be significantly altered in MFS patients compared to controls (> 2.0-fold change, adjusted P < 0.05). The expression of 11 miRNA and 6 mRNA candidates was validated by RT-qPCR in an independent cohort of 26 MFS patients and 26 matched HV controls. Significant inverse correlations were evident between 8 miRNAs and 5 mRNAs involved in vascular pathology, inflammation and telomerase regulation. Significant positive correlations were present for 7 miRNAs with age, for 2 miRNAs with the MFS aortic root status (Z-score) and for 7 miRNAs with left ventricular end-diastolic diameter in MFS patients. In addition, miR-331-3p was significantly up-regulated in MFS patients without mitral valve prolapse (MVP) as compared with patients with MVP. CONCLUSIONS:Our data show deregulated gene and miRNA expression profiles in the peripheral blood of MFS patients, demonstrating several candidates for prognostic biomarkers for cardiovascular manifestations in MFS as well as targets for novel therapeutic approaches. A deregulation of miRNA expression seems to play an important role in MFS, highlighting the plethora of effects on post-transcriptional regulation of miRNAs and mRNAs initiated by constitutional mutations in single genes. Trial registration Nr: EA2/131/10 . Registered 28 December, 2010.

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Prognostic impact of peripheral blood WT1-mRNA expression in patients with MDS.

Publications

Prognostic impact of peripheral blood WT1-mRNA expression in patients with MDS.

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