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

Clin Chem Lab Med. 2016 May;54(5):865-71. doi: 10.1515/cclm-2015-0536.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / analysis
  • Cohort Studies
  • DNA Methylation*
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Myelodysplastic Syndromes / diagnosis*
  • Myelodysplastic Syndromes / genetics*
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Transcription Factors / genetics*
  • Young Adult

Substances

  • Biomarkers
  • DLX4 protein, human
  • Homeodomain Proteins
  • Transcription Factors