An Adaptive Transfer-Learning-Based Deep Cox Neural Network for Hepatocellular Carcinoma Prognosis Prediction

Abstract

Background Predicting hepatocellular carcinoma (HCC) prognosis is important for treatment selection, and it is increasingly interesting to predict prognosis through gene expression data. Currently, the prognosis remains of low accuracy due to the high dimension but small sample size of liver cancer omics data. In previous studies, a transfer learning strategy has been developed by pre-training models on similar cancer types and then fine-tuning the pre-trained models on the target dataset. However, transfer learning has limited performance since other cancer types are similar at different levels, and it is not trivial to balance the relations with different cancer types. Methods Here, we propose an adaptive transfer-learning-based deep Cox neural network (ATRCN), where cancers are represented by 12 phenotype and 10 genotype features, and suitable cancers were adaptively selected for model pre-training. In this way, the pre-trained model can learn valuable prior knowledge from other cancer types while reducing the biases. Results ATRCN chose pancreatic and stomach adenocarcinomas as the pre-training cancers, and the experiments indicated that our method improved the C-index of 3.8% by comparing with traditional transfer learning methods. The independent tests on three additional HCC datasets proved the robustness of our model. Based on the divided risk subgroups, we identified 10 HCC prognostic markers, including one new prognostic marker, TTC36. Further wet experiments indicated that TTC36 is associated with the progression of liver cancer cells. Conclusion These results proved that our proposed deep-learning-based method for HCC prognosis prediction is robust, accurate, and biologically meaningful.