Cox-Sage: enhancing Cox proportional hazards model with interpretable graph neural networks for cancer prognosis.

Abstract

High-throughput sequencing technologies have facilitated a deeper exploration of prognostic biomarkers. While many deep learning (DL) methods primarily focus on feature extraction or employ simplistic fully connected layers within prognostic modules, the interpretability of DL-extracted features can be challenging. To address these challenges, we propose an interpretable cancer prognosis model called Cox-Sage. Specifically, we first propose an algorithm to construct a patient similarity graph from heterogeneous clinical data, and then extract protein-coding genes from the patient's gene expression data to embed them as features into the graph nodes. We utilize multilayer graph convolution to model proportional hazards pattern and introduce a mathematical method to clearly explain the meaning of our model's parameters. Based on this approach, we propose two metrics for measuring gene importance from different perspectives: mean hazard ratio and reciprocal of the mean hazard ratio. These metrics can be used to discover two types of important genes: genes whose low expression levels are associated with high cancer prognosis risk, and genes whose high expression levels are associated with high cancer prognosis risk. We conducted experiments on seven datasets from TCGA, and our model achieved superior prognostic performance compared with some state-of-the-art methods. As a primary research, we performed prognostic biomarker discovery on the LIHC (Liver Hepatocellular Carcinoma) dataset. Our code and dataset can be found at https://github.com/beeeginner/Cox-sage.