NDRG2 and TLR7 as novel DNA methylation prognostic signatures for acute myelocytic leukemia

J Cell Physiol. 2020 Apr;235(4):3790-3797. doi: 10.1002/jcp.29273. Epub 2019 Oct 15.

Abstract

Acute myelocytic leukemia (AML) is an aggressive malignant tumor and typically fatal without treatment. Identification and development of novel biomarkers could be beneficial for the diagnosis and prognosis of AML patients. Here, we aimed to identify the accurate DNA methylation prognostic signatures for AML patients. The DNA methylation data of AML patients and corresponding clinical information were retrieved from The Cancer Genome Atlas database. CPG sites that correlates closely with the survival of the AML patients were identified and further combined into CPG sites pairs to screen the survival-related pairs. The prognostic signatures were identified by the C-index and forward search algorithms and validated by the verification group. Finally, the functional enrichment analysis was performed on these CPG sites. As a result, a total of 498 CPG sites associated with the overall survival of AML patients was obtained. A prognostic signature composed of 10 CPG sites pairs was obtained and validated. The functional enrichment analysis showed prognostic genes were mainly enriched in tumor protein processing, cell differentiation, blood leukocyte immunity, and platelet growth factor pathways. In summary, we identified two accurate prognostic methylation signatures (NDRG2 and TLR7), which would be served as a novel therapy target for AML.

Keywords: AML; NDRG2; TLR7; methylation signature; prognostic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / epidemiology
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / pathology
  • Male
  • Middle Aged
  • Toll-Like Receptor 7 / genetics*
  • Tumor Suppressor Proteins / genetics*

Substances

  • NDRG2 protein, human
  • TLR7 protein, human
  • Toll-Like Receptor 7
  • Tumor Suppressor Proteins