Establishment and Validation of a Recurrent Prediction Model for Glioma: Extrinsic Apoptotic Molecules FADD and CASP8 Are Closely Associated With Glioma Recurrence

Lei Yang ^1* Li Lanying ² YanFang Zhang ^1*

• ¹ Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
• ² Institute of Cancer, Xinqiao Hospital, Army Medical University, Chongqing, China

Background: Glioma is the most common lethal tumor of the human brain. The presence of tumor heterogeneity, the tumor microenvironment and drug resistance make gliomas inevitable for recurrence. It is of great importance to learn about the risk factors and underlying mechanisms of glioma recurrence and progression. In this study, we aimed to create a tumor recurrent-based prediction model to predict recurrence and survival as well as to reveal the potential possible mechanisms of recurrence in patients with glioma.Methods: The gene expression data and clinicopathologic features were from the Chinese Glioma Genome Atlas (CGGA) database. The CGGA 693 database was used as the training group, and the CGGA 325 database was used as the validation group. LASSO regression has been performed to build a prognostic model. Cox regression and Kaplan-Meier survival curves were performed to investigate the prognostic value. Functional analyses were carried out by Gene Ontology Analysis, Gene Set Variation Analysis (GSVA), and pearson analysis. The potential pathological factors apoptosis for recurrence were further analysed in the follow-up. The R language was used as the main tool for statistical analysis and graphical work.Results: The 9-recurrent genes related signature has been established. The results showed the recurrent score could be considered as an independent predictor for glioma patients. Moreover, function analysis of the predictive recurrent signature exhibited that the signature was associated with apoptosis. Further studies have shown that extrinsic, but not intrinsic apoptotic molecules are strongly associated with glioma recurrence.Conclusions: The prediction model based on these 9 key genes can better identify the high-risk and low-risk groups of glioma recurrence, which lays a solid foundation for assessing the risk of glioma recurrence. And our study found that apoptosis is closely related to glioma recurrence, especially extrinsic apoptotic molecules FADD and CASP8, which provides a potential possible mechanism for glioma recurrence.