Determining the prognosis of Lung cancer from mutated genes using a deep learning survival model: a large multi-center study

Background Gene status has become the focus of prognosis prediction. Furthermore, deep learning has frequently been implemented in medical imaging to diagnose, prognosticate, and evaluate treatment responses in patients with cancer. However, few deep learning survival (DLS) models based on mutational genes that are directly associated with patient prognosis in terms of progression-free survival (PFS) or overall survival (OS) have been reported. Additionally, DLS models have not been applied to determine IO-related prognosis based on mutational genes. Herein, we developed a deep learning method to predict the prognosis of patients with lung cancer treated with or without immunotherapy (IO). Methods Samples from 6542 patients from different centers were subjected to genome sequencing. A DLS model based on multi-panels of somatic mutations was trained and validated to predict OS in patients treated without IO and PFS in patients treated with IO. Results In patients treated without IO, the DLS model (low vs. high DLS) was trained using the training MSK-MET cohort (HR = 0.241 [0.213–0.273], P < 0.001) and tested in the inter-validation MSK-MET cohort (HR = 0.175 [0.148–0.206], P < 0.001). The DLS model was then validated with the OncoSG, MSK-CSC, and TCGA-LUAD cohorts (HR = 0.420 [0.272–0.649], P < 0.001; HR = 0.550 [0.424–0.714], P < 0.001; HR = 0.215 [0.159–0.291], P < 0.001, respectively). Subsequently, it was fine-tuned and retrained in patients treated with IO. The DLS model (low vs. high DLS) could predict PFS and OS in the MIND, MSKCC, and POPLAR/OAK cohorts ( P < 0.001, respectively). Compared with tumor-node-metastasis staging, the COX model, tumor mutational burden, and programmed death-ligand 1 expression, the DLS model had the highest C-index in patients treated with or without IO. Conclusions The DLS model based on mutational genes can robustly predict the prognosis of patients with lung cancer treated with or without IO.