A risk signature with four autophagy-related genes for predicting survival of glioblastoma multiforme

Abstract

Glioblastoma multiforme (GBM) is a devastating brain tumour without effective treatment. Recent studies have shown that autophagy is a promising therapeutic strategy for GBM. Therefore, it is necessary to identify novel biomarkers associated with autophagy in GBM. In this study, we downloaded autophagy-related genes from Human Autophagy Database (HADb) and Gene Set Enrichment Analysis (GSEA) website. Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis were performed to identify genes for constructing a risk signature. A nomogram was developed by integrating the risk signature with clinicopathological factors. Time-dependent receiver operating characteristic (ROC) curve and calibration plot were used to evaluate the efficiency of the prognostic model. Finally, four autophagy-related genes (DIRAS3, LGALS8, MAPK8 and STAM) were identified and were used for constructing a risk signature, which proved to be an independent risk factor for GBM patients. Furthermore, a nomogram was developed based on the risk signature and clinicopathological factors (IDH1 status, age and history of radiotherapy or chemotherapy). ROC curve and calibration plot suggested the nomogram could accurately predict 1-, 3- and 5-year survival rate of GBM patients. For function analysis, the risk signature was associated with apoptosis, necrosis, immunity, inflammation response and MAPK signalling pathway. In conclusion, the risk signature with 4 autophagy-related genes could serve as an independent prognostic factor for GBM patients. Moreover, we developed a nomogram based on the risk signature and clinical traits which was validated to perform better for predicting 1-, 3- and 5-year survival rate of GBM.

Keywords: autophagy; glioblastoma multiform; nomogram; prognosis; risk signature.