GSE263890 Combined bioinformatic and clinical assay uncovers resistance and susceptibility mechanisms of human glioblastomas to temozolomide and identifies new survival biomarkers outperforming MGMT promoter methylation

Contributors : Maria Suntsova ; Alexander Modestov ; Anton BuzdinSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensGlioblastoma (GBM) is the most aggressive and lethal CNS tumor with only 14 months median overall survival after diagnosis and ∼5% 5-years survival rate. The treatment strategy is mainly surgery and/or radiation therapy, both combined with adjuvant temozolomide (TMZ) chemotherapy. TMZ treatment results in methylation of DNA purine bases, where the primary cytotoxic lesion is O6-methylguanine that can be removed by DNA rep air enzyme methylguanine methyltransferase (MGMT) when tumors express this protein. Historically, methylation of MGMT gene promoter is used as the major biomarker predicting individual tumor response to TMZ, but there are also additional biomarkers. However, most of them were developed using TCGA pr oject collection of molecular profiles which were unproperly diagnosed as GBM and now need to be reclassified according to the most recent WHO CNS5 tumor classification. Here we for the first time compared biomarker potentials of MGMT methylation, expression levels of 361 DNA repair genes, and activ ation levels of 38 DNA repair pathways on updated TCGA and other samplings and validated the results on our experimental multicenter GBM patient cohort (n=50). We found that expression/activation levels of 7 and 6 emerging gene/pathway biomarkers served as high-quality positive (HR1.63), respectively, patient surv...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research