ICAR: endoscopic skull‐base surgery

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<it>MGMT</it>, <it>GATA6</it>, <it>CD81</it>, <it>DR4</it>, and <it>CASP8</it> gene promoter methylation in glioblastoma

<p>Abstract</p> <p>Background</p> <p>Methylation of promoter region is the major mechanism affecting gene expression in tumors. Recent methylome studies of brain tumors revealed a list of new epigenetically modified genes. Our aim was to study promoter methylation of newly identified epigenetically silenced genes together with already known epigenetic markers and evaluate its separate and concomitant role in glioblastoma genesis and patient outcome.</p> <p>Methods</p> <p>The methylation status of <it>MGMT</it>, <it>CD81</it>, <it>GATA6</it>, <it>DR4</it>, and <it>CASP8</it> in 76 patients with primary glioblastomas was investigated. Methylation-specific PCR reaction was performed using bisulfite treated DNA. Evaluating glioblastoma patient survival time after operation, patient data and gene methylation effect on survival was estimated using survival analysis.</p> <p>Results</p> <p>The overwhelming majority (97.3%) of tumors were methylated in at least one of five genes tested. In glioblastoma specimens gene methylation was observed as follows: <it>MGMT</it> in 51.3%, <it>GATA6</it> in 68.4%, <it>CD81</it> in 46.1%, <it>DR4</it> in 41.3% and <it>CASP8</it> in 56.8% of tumors. Methylation of <it>MGMT</it> was associated with younger patient age (p < 0.05), while <it>CASP8</it> with older (p < 0.01). <it>MGMT</it> methylation was significantly more frequent event in patient group who survived longer than 36 months after operation (p < 0.05), while methylation of <it>CASP8</it> was more frequent in patients who survived shorter than 36 months (p < 0.05). Cox regression analysis showed patient age, treatment, <it>MGMT</it>, <it>GATA6</it> and <it>CASP8</it> as independent predictors for glioblastoma patient outcome (p < 0.05). <it>MGMT</it> and <it>GATA6</it> were independent predictors for patient survival in younger patients’ group, while there were no significant associations observed in older patients’ group when adjusted for therapy.</p> <p>Conclusions</p> <p>High methylation frequency of tested genes shows heterogeneity of glioblastoma epigenome and the importance of <it>MGMT</it>, <it>GATA6</it> and <it>CASP8</it> genes methylation in glioblastoma patient outcome.</p