Startseite Hypermethylation of DLX4 predicts poor clinical outcome in patients with myelodysplastic syndrome
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Hypermethylation of DLX4 predicts poor clinical outcome in patients with myelodysplastic syndrome

  • Ting-juan Zhang , Jing-dong Zhou , Dong-qin Yang , Yu-xin Wang , Dong-ming Yao , Ji-chun Ma , Xiang-mei Wen , Hong Guo , Jiang Lin EMAIL logo und Jun Qian EMAIL logo
Veröffentlicht/Copyright: 20. Oktober 2015
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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.


Corresponding authors: Jun Qian, MD, Department of Hematology, Affiliated People’s Hospital of Jiangsu University, 8 Dianli Rd., 212002 Zhenjiang, P.R. China, Fax: +86 511 85234387, E-mail: ; and Jiang Lin, PhD, Laboratory Center, Affiliated People’s Hospital of Jiangsu University, 8 Dianli Rd., 212002 Zhenjiang, P.R. China, Fax: +86 511 85234387, E-mail:
aTing-juan Zhang and Jing-dong Zhou contributed equally to this work.

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).

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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.


Received: 2015-6-9
Accepted: 2015-9-25
Published Online: 2015-10-20
Published in Print: 2016-5-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

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