Glioblastoma multiforme is a deadly brain cancer with a median patient survival time of 18-24 months, despite aggressive treatments. This limited success is due to a combination of aggressive tumor behavior, genetic heterogeneity of the disease within a single patient’s tumor, resistance to therapy, and lack of precision medicine treatments. A single specimen using a biopsy cannot be used for complete assessment of the tumor’s microenvironment, making personalized care limited and challenging. Temozolomide (TMZ) is a commercially approved alkylating agent used to treat glioblastoma, but around 50% of temozolomide-treated patients do not respond to it due to the over-expression of O6-methylguanine methyltransferase (MGMT). MGMT is a DNA repair enzyme that rescues tumor cells from alkylating agent-induced damage, leading to resistance to chemotherapy drugs. Epigenetic silencing of the MGMT gene by promoter methylation results in decreased MGMT protein expression, reduced DNA repair activity, increased sensitivity to TMZ, and longer survival time. Thus, it is paramount that clinicians determine the methylation status of patients to provide personalized chemotherapy drugs. However, current methods for determining this via invasive biopsies or manually curated features from brain MRI (Magnetic Resonance Imaging) scans are time- and cost- intensive, and have a very low accuracy. Authors present a novel approach of using convolutional neural networks to predict methylation status and recommend patient-specific treatments via an analysis of brain MRI scans. The authors have developed an AI platform, GLIA-Deep, using a U-Net architecture and a ResNet-50 architecture trained on genomic data from TCGA (The Cancer Genome Atlas through the National Cancer Institute) and brain MRI scans from TCIA (The Cancer Imaging Archive). GLIA-Deep performs tumor region identification and determines MGMT methylation status with 90% accuracy in less than 5 seconds, a real-time analysis that eliminates huge time and cost investments of invasive biopsies. Using computational modeling, the analysis further recommends microRNAs that modulate MGMT gene expression by translational repression to make glioma cells TMZ sensitive, thereby improving the survival of glioblastoma patients with unmethylated MGMT. GLIA-Deep is a completely integrated, end-to-end, cost-effective and time-efficient platform that advances precision medicine by recommending personalized therapies from an analysis of individual MRI scans to improving glioblastoma treatment options.
MRI-BASED DEEP LEARNING METHOD FOR DETERMINING METHYLATION STATUS OF THE O6-METHYLGUANINE–DNA METHYLTRANSFERASE PROMOTER OUTPERFORMS TISSUE BASED METHODS IN BRAIN GLIOMAS