  The diagnosis and prognosis of cancer are typically based on multi-modal
clinical data, including histology images and genomic data, due to the complex
pathogenesis and high heterogeneity. Despite the advancements in digital
pathology and high-throughput genome sequencing, establishing effective
multi-modal fusion models for survival prediction and revealing the potential
association between histopathology and transcriptomics remains challenging. In
this paper, we propose Pathology-Genome Heterogeneous Graph (PGHG) that
integrates whole slide images (WSI) and bulk RNA-Seq expression data with
heterogeneous graph neural network for cancer survival analysis. The PGHG
consists of biological knowledge-guided representation learning network and
pathology-genome heterogeneous graph. The representation learning network
utilizes the biological prior knowledge of intra-modal and inter-modal data
associations to guide the feature extraction. The node features of each
modality are updated through attention-based graph learning strategy. Unimodal
features and bi-modal fused features are extracted via attention pooling module
and then used for survival prediction. We evaluate the model on low-grade
gliomas, glioblastoma, and kidney renal papillary cell carcinoma datasets from
the Cancer Genome Atlas (TCGA) and the First Affiliated Hospital of Zhengzhou
University (FAHZU). Extensive experimental results demonstrate that the
proposed method outperforms both unimodal and other multi-modal fusion models.
For demonstrating the model interpretability, we also visualize the attention
heatmap of pathological images and utilize integrated gradient algorithm to
identify important tissue structure, biological pathways and key genes.
