A comprehensive prognostic signature for glioblastoma patients based on transcriptomics and single cell sequencing

PURPOSE: Glioblastoma (GBM) is the most common and deadly brain tumor. We aimed to reveal potential prognostic GBM marker genes, elaborate their functions, and build an effective a prognostic model for GBM patients. METHODS: Through data mining of The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we screened for significantly differentially expressed genes (DEGs) to calculate risk scores for individual patients. Published data of somatic mutation and copy number variation profiles were analyzed for distinct genomic alterations associated with risk scores. In addition, single-cell sequencing was used to explore the biological functions of the identified prognostic marker genes. By combining risk scores and other clinical features, we built a comprehensive prognostic GBM model. RESULTS: Seven DEGs (CLEC5A, HOXC6, HOXA5, CCL2, GPRASP1, BSCL2 and PTX3) were identified as being prognostic for GBM. Expression of these genes was confirmed in different GBM cell lines using real-time PCR. Risk scores calculated from the seven DEGs revealed prognostic value irrespective of other clinical factors, including IDH mutation status, and were negatively correlated with TP53 expression. The prognostic genes were found to be associated with tumor proliferation and progression based on pseudo-time analysis in neoplastic cells. A final prognostic model was developed and validated with a good performance, especially in geriatric GBM patients. CONCLUSIONS: Using genetic profiles, age, IDH mutation status, and chemotherapy and radiotherapy, we constructed a comprehensive prognostic model for GBM patients. The model has a good performance, especially in geriatric GBM patients.