A transformer-based deep learning survival prediction model and an explainable XGBoost anti-PD-1/PD-L1 outcome
Ren Wang1,2,3, Qiumei Liu1,2,3, Wenhua You1,2,3
1The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Department of Immunology, School of Basic Medical Sciences, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, Jiangsu Province, China.
Abstract:
Recent studies suggest cGAS-STING pathway may play a crucial role in the genesis and development of hepatocellular carcinoma (HCC), closely associated with classical pathways and tumor immunity. We aimed to develop models predicting survival and anti-PD-1/PD-L1 outcomes centered on the cGAS-STING pathway in HCC. We identified classical pathways highly correlated with cGAS-STING pathway and constructed transformer survival model preserving raw structure of pathways. We also developed explainable XGBoost model for predicting anti-PD-1/PD-L1 outcomes using SHAP algorithm. We trained and validated transformer survival model on pan-cancer cohort and tested it on three independent HCC cohorts. Using 0.5 as threshold across cohorts, we divided each HCC cohort into two groups and calculated P values with log-rank test. TCGA-LIHC: C-index = 0.750, P = 1.52e-11; ICGC-LIRI-JP: C-index = 0.741, P = .00138; GSE144269: C-index = 0.647, P = .0233. We trained and validated [area under the receiver operating characteristic curve (AUC) = 0.777] XGBoost model on immunotherapy datasets and tested it on GSE78220 (AUC = 0.789); we also tested XGBoost model on HCC anti-PD-L1 cohort (AUC = 0.719). Our deep learning model and XGBoost model demonstrate potential in predicting survival risks and anti-PD-1/PD-L1 outcomes in HCC. We deployed these two prediction models to the GitHub repository and provided detailed instructions for their usage: deep learning survival model, https://github.com/mlwalker123/CSP_survival_model; XGBoost immunotherapy model, https://github.com/mlwalker123/CSP_immunotherapy_model.
