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Journal of Neuro-Oncology

, Volume 140, Issue 3, pp 559–568 | Cite as

Defining a prognostic score based on O6-methylguanine-DNA methyltransferase cut-off methylation level determined by pyrosequencing in patients with glioblastoma multiforme

  • Elisa De Carlo
  • Lorenzo Gerratana
  • Giovanna De Maglio
  • Vanessa Buoro
  • Francesco Cortiula
  • Lorena Gurrieri
  • Miriam Isola
  • Gianpiero Fasola
  • Fabio Puglisi
  • Stefano Pizzolitto
  • Simona Rizzato
Clinical Study

Abstract

Purpose

Epigenetic variations in the O6-methylguanine-methyltransferase gene had been widely associated with a favorable impact on survival in patients affected by glioblastoma multiforme (GBM). Aim of this study is to explore a scoring system based on the gene promoter methylation in order to predict patients’ prognosis.

Methods

A series of 128 patients with GBM was retrospectively analyzed. A training set and a validations set were then generated. The methylation level of CpGi from 74 to 83 was determined by pyrosequencing. In accordance to previous literature, each island was assigned with 1 point if the corresponding methylation level was higher than 9%. The sum consisted in a score that went from 0 (all CpGi < 9%) to 10 (all CpGi ≥ 9%). A threshold capable to detect a favorable outcome (overall survival, OS > 24 months) was identified by ROC analysis.

Results

Median OS and follow-up were 14 and 32.6 months respectively. Among the total population, 35% of the pts had a score of 0, while 29% had a score of 10. A score ≥ 6 was associated with a favorable prognosis also when corrected for age (> 70 vs. ≤ 70 years) and ECOG performance status (0–1 vs. 2–3). Similar results were observed also in terms of PFS. Results were consistent in the training and in the validation set.

Conclusions

The present manuscript explored a novel scoring system capable to take into consideration the methylation status of each single CpGi, capable to better predict prognosis in GBM patients.

Keywords

Glioblastoma multiforme Prognostic score MGMT cut-off methylation level CpG islands 

Notes

Acknowledgements

No person other than the authors contributed to this work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study, whenever possible, taking in account the retrospective nature of the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Elisa De Carlo
    • 1
    • 2
  • Lorenzo Gerratana
    • 1
    • 3
  • Giovanna De Maglio
    • 4
  • Vanessa Buoro
    • 1
    • 3
  • Francesco Cortiula
    • 1
    • 3
  • Lorena Gurrieri
    • 5
  • Miriam Isola
    • 3
  • Gianpiero Fasola
    • 1
  • Fabio Puglisi
    • 2
    • 3
  • Stefano Pizzolitto
    • 4
  • Simona Rizzato
    • 1
  1. 1.Department of OncologyUniversity Hospital of UdineUdineItaly
  2. 2.Department of Clinical OncologyIRCCS CRO Aviano National Cancer InstituteAvianoItaly
  3. 3.Department of Medicine (DAME)The University of UdineUdineItaly
  4. 4.Department of PathologyUniversity Hospital of UdineUdineItaly
  5. 5.Department of OncologyASUITS University HospitalTriesteItaly

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