Prognostic relevance of SOCS3 hypermethylation in patients with glioblastoma multiforme

Maurizio Martini, Roberto Pallini, Luigi Maria Larocca, Tonia Cenci, Corrado Lucantoni, Giuseppe Luongo

Risultato della ricerca: Contributo in rivistaArticolo in rivista

54 Citazioni (Scopus)

Abstract

Alterations in the signal transduction pathways are key mechanisms in the pathogenesis of de novo glioblastoma multiforme (GBM), which are also involved in the resistance to chemo- and radiotherapy. Here, we analyzed the methylation status and mRNA expression of suppressor of cytokine signaling (SOCS)1-2-3, 3 of the most important inhibitory molecules of the signal transduction circuitry, in 46 GBM specimens. The relationship between methylation status of SOCS1-2-3 and clinical outcome was investigated. Using methylation-specific PCR (MS-PCR) and sequencing, after bisulphite modification, we found that the promoter of SOCS1-2-3 was methylated in 24, 6.5 and 35% of GBM, respectively. Real-time analysis showed that in methylated GBM, mRNA expression for SOCS1-2-3 was reduced by 5, 3 and 7-folds, respectively, when compared with unmethylated GBM. Moreover, methylation of SOCS3 promoter significantly associated with an unfavorable clinical outcome (p < 0.0002). Our data suggest that methylation of SOCS3 may be involved in the pathogenesis of GBM and in the resistance of this neoplasm to conventional treatment.
Lingua originaleEnglish
pagine (da-a)2955-2960
Numero di pagine6
RivistaInternational Journal of Cancer
Volume123
DOI
Stato di pubblicazionePubblicato - 2008

Keywords

  • Adult
  • Aged
  • DNA Methylation
  • DNA Modification Methylases
  • DNA Repair Enzymes
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Prognosis
  • Promoter Regions, Genetic
  • RNA, Messenger
  • Suppressor of Cytokine Signaling Proteins
  • Tumor Suppressor Proteins

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