Artificial neural network identified a 20‐gene panel in predicting immunotherapy response and survival benefits after anti‐PD1/PD‐L1 treatment in glioblastoma patients

Abstract

Abstract Background Immune checkpoint inhibitors (ICIs) are a promising immunotherapy approach, but glioblastoma clinical trials have not yielded satisfactory results. Objective To screen glioblastoma patients who may benefit from immunotherapy. Methods Eighty‐one patients receiving anti‐PD1/PD‐L1 treatment from a large‐scale clinical trial and 364 patients without immunotherapy from The Cancer Genome Atlas (TCGA) were included. Patients in the ICI‐treated cohort were divided into responders and nonresponders according to overall survival (OS), and the most critical responder‐relevant features were screened using random forest (RF). We constructed an artificial neural network (ANN) model and verified its predictive value with immunotherapy response and OS. Results We defined two groups of ICI‐treated glioblastoma patients with large differences in survival benefits as nonresponders (OS ≤6 months, n = 18) and responders (OS ≥17 months, n = 8). No differentially mutated genes were observed between responders and nonresponders. We performed RF analysis to select the most critical responder‐relevant features and developed an ANN with 20 input variables, five hidden neurons and one output neuron. Receiver operating characteristic analysis and the DeLong test demonstrated that the ANN had the best performance in predicting responders, with an AUC of 0.97. Survival analysis indicated that ANN‐predicted responders had significantly better OS rates than nonresponders. Conclusion The 20‐gene panel developed by the ANN could be a promising biomarker for predicting immunotherapy response and prognostic benefits in ICI‐treated GBM patients and may guide oncologists to accurately select potential responders for the preferential use of ICIs.

Keywords

• artificial neural network model
• glioblastoma
• immune checkpoint inhibitor
• immunotherapy