Hypermethylation of DLX4 predicts poor clinical outcome in patients with myelodysplastic syndrome
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Ting-juan Zhang
und Jun Qian
Abstract
Background:
Hypermethylation of DLX4 (distal-less homeobox 4) has been disclosed in a variety of cancers. Our work was aimed to examine the pattern of DLX4 methylation and further investigate its clinical relevance in patients with myelodysplastic syndrome (MDS).
Methods:
Real-time quantitative methylation-specific PCR and bisulfite sequencing PCR were carried out to detect the level of DLX4 methylation. Clinical significance of DLX4 methylation was analyzed between the DLX4 hypermethylated and non-hypermethylated patients.
Results:
DLX4 was significantly hypermethylated in MDS patients than controls (p<0.001). No significant differences were observed between the hypermethylated and non-hypermethylated MDS patients in white blood cells, platelets, age, WHO classifications, FAB classifications, IPSS risks, and common gene mutations (p>0.05). However, DLX4 hypermethylated patients tended to have higher hemoglobin (HB) than DLX4 non-hypermethylated patients (p=0.079). Moreover, there was a trend that male patients, poor karyotype patients, and IPSS Int-2/High patients had a higher frequency of DLX4 hypermethylation (p=0.067, 0.065, and 0.068). DLX4 hypermethylated patients had significantly shorter overall survival than DLX4 non-hypermethylated patients (p=0.004). Multivariate analysis confirmed the prognostic value of DLX4 methylation in MDS patients (p<0.001).
Conclusions:
Our study indicated that DLX4 hypermethylation was a frequent event and acted as an independent prognostic biomarker in de novo MDS patients.
Acknowledgments
This study was supported by National Natural Science foundation of China (81270630, 81172592), Science and Technology Special Project in Clinical Medicine of Jiangsu Province (BL2012056), 333 Project of Jiangsu Province (BRA2013136), Medical Key Talent Project of Zhenjiang, Social Development Foundation of Zhenjiang (SH2013082, SH2014044, SH2014086).
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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Supplemental Material:
The online version of this article (DOI: 10.1515/cclm-2015-0536) offers supplementary material, available to authorized users.
©2016 Walter de Gruyter GmbH, Berlin/Boston
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- Frontmatter
- Editorial
- Protein S100B: from cancer diagnostics to the evaluation of mild traumatic brain injury
- Reviews
- Capillary electrophoresis based on nucleic acid detection for diagnosing human infectious disease
- Oxidative damage and the pathogenesis of menopause related disturbances and diseases
- Opinion Paper
- EFLM WG-Preanalytical phase opinion paper: local validation of blood collection tubes in clinical laboratories
- Genetics and Molecular Diagnostics
- Effective quality management practices in routine clinical next-generation sequencing
- Analysis of PMP22 duplication and deletion using a panel of six dinucleotide tandem repeats
- A novel exonuclease (TaqMan) assay for rapid haptoglobin genotyping
- General Clinical Chemistry and Laboratory Medicine
- Heparinate but not serum tubes are susceptible to hemolysis by pneumatic tube transportation
- Criteria of adequacy for vitamin D testing and prevalence of deficiency in clinical practice
- A simple clot based assay for detection of procoagulant cell-derived microparticles
- Measurement of factor XIII (FXIII) activity by an automatic ammonia release assay using iodoacetamide blank-procedure: no more overestimation in the low activity range and better detection of severe FXIII deficiencies
- Immunoassay or LC-MS/MS for the measurement of salivary cortisol in children?
- Head to head evaluation of the analytical performance of two commercial methotrexate immunoassays and comparison with liquid chromatography-mass spectrometry and the former fluorescence polarization immunoassay
- Reference Values and Biological Variations
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- Cardiovascular Diseases
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- Platelet volume is associated with the Framingham risk score for cardiovascular disease in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
- Infectious Diseases
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