Identification of WHO II/III Gliomas by 16 Prognostic-related Gene Signatures using Machine Learning Methods

Background: It is found that the prognosis of gliomas of the same grade has large differences among World Health Organization (WHO) grade II and III in clinical observation. Therefore, a better understanding of the genetics and molecular mechanisms underlying WHO grade II and III gliomas is required, with the aim of developing a classi-fication scheme at the molecular level rather than the conventional pathological morphol-ogy level. Methods: We performed survival analysis combined with machine learning methods of Least Absolute Shrinkage and Selection Operator using expression datasets downloaded from the Chinese Glioma Genome Atlas as well as The Cancer Genome Atlas. Risk scores were calculated by the product of expression level of overall survival-related genes and their multivariate Cox proportional hazards regression coefficients. WHO grade II and III gliomas were categorized into the low-risk subgroup, medium-risk subgroup, and high-risk subgroup. We used the 16 prognostic-related genes as input features to build a classification model based on prognosis using a fully connected neural network. Gene function annotations were also performed. Results: The 16 genes (AKNAD1, C7orf13, CDK20, CHRFAM7A, CHRNA1, EFNB1, GAS1, HIST2H2BE, KCNK3, KLHL4, LRRK2, NXPH3, PIGZ, SAMD5, ERINC2, and SIX6) related to the glioma prognosis were screened. The 16 selected genes were associ-ated with the development of gliomas and carcinogenesis. The accuracy of an external validation data set of the fully connected neural network model from the two cohorts reached 95.5%. Our method has good potential capability in classifying WHO grade II and III gliomas into low-risk, medium-risk, and high-risk subgroups. The subgroups showed significant (P<0.01) differences in overall survival. Conclusion: This resulted in the identification of 16 genes that were related to the prog-nosis of gliomas. Here we developed a computational method to discriminate WHO grade II and III gliomas into three subgroups with distinct prognoses. The gene expression-based method provides a reliable alternative to determine the prognosis of gliomas.