Survival Risk Prediction Models of Gliomas Based on IDH and 1p/19q

Abstract

Gliomas have been classified into different molecular subtypes based on their molecular features. To explore the prognostic factors of different subtypes of gliomas, we performed a univariate survival analysis based on the RNA-seq data of 653 patients obtained from The Cancer Genome Atlas. We identified 12205 (20.18%), 6125 (10.13%) and 5206 (8.61%) genes associated with the overall survival (OS) of the IDH-wildtype, IDH-mutation 1p/19q intact and IDH-mutation 1p/19q codeletion gliomas, respectively. Pathway enrichment analysis revealed that OS related genes were mainly involved in alcoholism, systemic lupus erythematosus, hematopoietic cell lineage and diabetes. The OS related genes were further selected using Lasso regression, and three prognostic risk score models were constructed to effectively predict the OS of the patients with different subtypes of gliomas. In total, 76 signature genes were identified and were selected to construct the three models. Moreover, neither of the 76 genes overlapped between different models, which suggested the enormous difference among the three subtypes, although some signature genes (SERPINA5, RP11.229A12.2 and RP11.62F24.2) were also identified as the OS related genes in different glioma subtypes. Interestingly, five genes (RP11.229A12.2, RP11.62F24.2, C3orf67, RP11.275H4.1 and TBX3) played opposing roles (protective or risk factor) in different subtypes. Additionally, the prognosis models consisted of a substantial proportion of non-coding RNA (58.74%, 70.13% and 58.11% in the IDH-wildtype, IDH-mutation 1p/19q intact and IDH-mutation 1p/19q codeletion). Furthermore, multivariate analysis integrating clinical variables demonstrated that risk group predicted by the prognostic models was an independent prognostic factor for gliomas. In conclusion, we have constructed and validated three models that have the potential to predict the prognosis of glioma patients. The genes and pathways identified in this study require further investigation for their underlying mechanisms and potential clinical significance in improving the OS of the glioma patients.

Clinical, pharmacological, and formulation evaluation of disulfiram in the treatment of glioblastoma - a systematic literature review

“…In 2013 is suggested to use as an adjunct to the Stupp Protocol [37]. Recently, Zou et al [38], performed a pathway enrichment analysis, suggesting, that alcoholism may share a common pathway with glioma, thus DS may have a proven effect in glioma treatment.…”