An epigenetic biomarker panel for glioblastoma multiforme personalized medicine through DNA methylation analysis of human embryonic stem cell-like signature

Jung Hsien Chiang, Wan Shu Cheng, Leroy Hood, Qiang Tian

研究成果: Article同行評審

18 引文 斯高帕斯(Scopus)

摘要

Alterations of DNA methylation occur during the course of both stem cell development and tumorigenesis. We present a novel strategy that can be used to stratify glioblastoma multiforme (GBM) patients through the epigenetic states of genes associated with human embryonic stem cell (hESC) identity in order to 1) assess linkages between the methylation signatures of these stem cell genes and survival of GBM patients, and 2) delineate putative mechanisms leading to poor prognosis in some patient subgroups. A DNA methylation signature was established for stratifying GBM patients into several hESC methylator subgroups. The hESC methylator-negative phenotype has demonstrated poor survival and upregulation of glioma stem cell (GSC) markers, and is enriched in one of the previously defined transcriptomic phenotypes - the mesenchymal phenotype. We further identified a refined signature of 36 genes as the gene panel, including SOX2, POU3F2, FGFR2, GAP43, NTRK2, NTRK3, and NKX2-2, which are highly enriched in the nervous system. Both signatures outperformed the O6-methylguanine-DNA methyltransferase (MGMT) methylation test in predicting patient's outcome. These findings were also validated through an independent dataset of patients. Furthermore, through statistical analyses, both signatures were examined significantly. Hypomethylation of hESC-associated genes predicted poorer clinical outcome in GBM, supporting the idea that epigenetic activation of stem cell genes contributes to GBM aggression. The gene panel presented herein may be developed into clinical assays for patient stratification and future personalized medicine interventions.

原文English
頁(從 - 到)310-323
頁數14
期刊OMICS A Journal of Integrative Biology
18
發行號5
DOIs
出版狀態Published - 2014 五月 1

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics

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