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Tumor Micro-environment Interactions Guided Graph Learning for Survival Analysis of Human Cancers from Whole-slide Pathological Images

The recent advance of deep learning technology brings the possibility of assisting the pathologist to predict the patients' survival from whole-slide pathological images (WSIs). However most of the prevalent methods only worked on the sampled patches in specifically or randomly selected tumor areas of WSIs which has very limited capability to capture the complex interactions between tumor and its surrounding micro-environment components. As a matter of fact tumor is supported and nurtured in the heterogeneous tumor micro-environment(TME) and the detailed analysis of TME and their correlation with tumors are important to in-depth analyze the mechanism of cancer development. In this paper we considered the spatial interactions among tumor and its two major TME components (i.e. lymphocytes and stromal fibrosis) and presented a Tumor Micro-environment Interactions Guided Graph Learning (TMEGL) algorithm for the prognosis prediction of human cancers. Specifically we firstly selected different types of patches as nodes to build graph for each WSI. Then a novel TME neighborhood organization guided graph embedding algorithm was proposed to learn node representations that can preserve their topological structure information. Finally a Gated Graph Attention Network is applied to capture the survival-associated intersections among tumor and different TME components for clinical outcome prediction. We tested TMEGL on three cancer cohorts derived from The Cancer Genome Atlas (TCGA) and the experimental results indicated that TMEGL not only outperforms the existing WSI-based survival analysis models but also has good explainable ability for survival prediction.

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