title: SOCS3 promoter hypermethylation is a favorable prognosticator and a novel indicator for G-CIMP-positive GBM patients.
abstract: BACKGROUND
  Hypermethylation of the suppressor of cytokine signaling 3(SOCS3) promoter has been reported to predict a poor prognosis in several cancers including glioblastoma multiforme (GBM). We explored the function of SOCS3 promoter hypermethylation in GBM cohorts, including analysis of the CpG island methylator phenotype (CIMP), when a large number of gene loci are simultaneously hypermethylated.
  
  
  METHODS
  A whole genome promoter methylation profile was performed in a cohort of 33 GBM samples, with 13 long-term survivors (LTS; overall survival ≥ 18 months) and 20 short-term survivors (STS; overall survival ≤ 9 months). The SOCS3 promoter methylation status was compared between the two groups. In addition, we investigated the relationship of SOCS3 promoter methylation and G-CIMP status.
  
  
  RESULTS
  Interestingly, in our present study, we found that SOCS3 promoter methylation was statistically significantly higher in the 13 LTS than that in the 20 STS. Furthermore, high SOCS3 promoter methylation detected via pyro-sequencing predicted a better prognosis in an independent cohort containing 62 GBM patients. This correlation was validated by the dataset from the Cancer Genome Atlas(TCGA) and the Chinese Cancer Genome Atlas(CGGA). In addition, we found that hypermethylation of the SOCS3 promoter was tightly associated with the G-CIMP-positive GBM patients.
  
  
  CONCLUSIONS
  Using a total of 359 clinical samples, we demonstrate that SOCS3 promoter hypermethylation status has a favorable prognostic value in GBM patients because of whole genome methylation status. Particularly, the hypermethylation of the SOCS3 promoter indicates positive G-CIMP status.
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Beijing Neurosurgical Institute, Beijing, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Beijing Neurosurgical Institute, Beijing, China.
authors.forename: Zhaoshi
authors.initials: Z
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Beijing Neurosurgical Institute, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Beijing Neurosurgical Institute, Beijing, China.
authors.forename: Gan
authors.initials: G
authors.lastname: You
authors.affiliation: Beijing Neurosurgical Institute, Beijing, China.
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Neurosurgical Institute, Beijing, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Beijing Neurosurgical Institute, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Institute of Basic Medical Sciences, Capital Medical University, Beijing, China.
authors.forename: Quangeng
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Beijing Neurosurgical Institute, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D005909:Glioblastoma / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*
chemical_list: C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins