Single-Cell Spatial Analysis of Histopathology Images for Survival Prediction via Graph Attention Network

The tumor microenvironment is a complex ecosystem consisting of various immune and stromal cells in addition to neoplastic cells. The spatial interaction and organization of these cells play a critical role in tumor progression. Single-cell analysis of histopathology images offers an intrinsic advantage over traditional patch-based approach by providing fine-grained cellular information. However, existing studies do not perform explicit cell classification, and therefore still suffer from limited interpretability and lack biological relevance, which may negatively affect the performance for clinical outcome prediction. To address these challenges, we propose a cell-level contextual learning approach to explicitly capture the major cell types and their spatial interaction in the tumor microenvironment. To do this, we first segmented and classified each cell into tumor cells, lymphocytes, fibroblasts, macrophages, neutrophils, and other nonmalignant cells on histopathology images. Given this single-cell map, we constructed a graph and trained a graph attention network to learn the cell-level contextual features for survival prediction. Extensive experiments demonstrate that our model consistently outperform existing patch-based and cell graph-based approaches in two independent datasets. Further, we used the feature attribution method to discover distinct spatial patterns that are associated with prognosis, leading to biologically meaningful and interpretable results.