Elisa De Carlo1,2, Lorenzo Gerratana3,4, Giovanna De Maglio5, Vanessa Buoro1,6, Francesco Cortiula1,6, Lorena Gurrieri7, Miriam Isola6, Gianpiero Fasola1, Fabio Puglisi2,6, Stefano Pizzolitto5, Simona Rizzato1. 1. Department of Oncology, University Hospital of Udine, P.le S.M. Misericordia, 15, 33100, Udine, Italy. 2. Department of Clinical Oncology, IRCCS CRO Aviano National Cancer Institute, Aviano, PN, Italy. 3. Department of Oncology, University Hospital of Udine, P.le S.M. Misericordia, 15, 33100, Udine, Italy. gerratana.lorenzo@spes.uniud.it. 4. Department of Medicine (DAME), The University of Udine, Udine, Italy. gerratana.lorenzo@spes.uniud.it. 5. Department of Pathology, University Hospital of Udine, Udine, Italy. 6. Department of Medicine (DAME), The University of Udine, Udine, Italy. 7. Department of Oncology, ASUITS University Hospital, Trieste, Italy.
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.
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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