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

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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.

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Data Avaliability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

No person other than the authors contributed to this work.

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Authors and Affiliations

  1. Department of Oncology, University Hospital of Udine, P.le S.M. Misericordia, 15, 33100, Udine, Italy

    Elisa De Carlo, Lorenzo Gerratana, Vanessa Buoro, Francesco Cortiula, Gianpiero Fasola & Simona Rizzato

  2. Department of Clinical Oncology, IRCCS CRO Aviano National Cancer Institute, Aviano, PN, Italy

    Elisa De Carlo & Fabio Puglisi

  3. Department of Medicine (DAME), The University of Udine, Udine, Italy

    Lorenzo Gerratana, Vanessa Buoro, Francesco Cortiula, Miriam Isola & Fabio Puglisi

  4. Department of Pathology, University Hospital of Udine, Udine, Italy

    Giovanna De Maglio & Stefano Pizzolitto

  5. Department of Oncology, ASUITS University Hospital, Trieste, Italy

    Lorena Gurrieri

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  1. Elisa De Carlo
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Correspondence to Lorenzo Gerratana.

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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.

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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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De Carlo, E., Gerratana, L., De Maglio, G. et al. Defining a prognostic score based on O6-methylguanine-DNA methyltransferase cut-off methylation level determined by pyrosequencing in patients with glioblastoma multiforme. J Neurooncol 140, 559–568 (2018). https://doi.org/10.1007/s11060-018-2981-7

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