RCoxNet: deep learning framework for enhanced cancer survival prediction integrating random walk with restart with mutation and clinical data

Cancer poses a significant global health challenge, characterized by a complex disease progression and disrupted growth regulation. A thorough understanding of cellular and molecular biological mechanisms is essential for developing novel treatments and improving the accuracy of patient survival predictions. While prior studies have leveraged gene expression and clinical data to forecast survival outcomes through current machine learning and deep learning approaches, gene mutation data—despite being a widely recognized metric—has rarely been incorporated due to its limited information, inadequate representation of gene relationships, and data sparsity, which negatively affects the robustness, effectiveness, and interpretability of current survival analysis approaches. To overcome the challenges of mutation data sparsity, we propose RCoxNet, a novel deep learning neural network framework that integrates the Random Walk with Restart (RWR) algorithm with a deep learning Cox Proportional Hazards model. By applying this framework to mutation data from cBioportal, our model achieved an average concordance index of 0.62 ± 0.05 across four cancer types, outperforming existing deep neural network models. Additionally, we identified clinical features critical for differentiating between predicted high- and low-risk patients, with the relevance of these features being partially supported by previous studies.