Integrative Histology-Genomic Analysis Predicts Hepatocellular Carcinoma Prognosis Using Deep Learning

Cancer prognosis analysis is of essential interest in clinical practice. In order to explore the prognostic power of computational histopathology and genomics, this paper constructs a multi-modality prognostic model for survival prediction. We collected 346 patients diagnosed with hepatocellular carcinoma (HCC) from The Cancer Genome Atlas (TCGA), each patient has 1-3 whole slide images (WSIs) and an mRNA expression file. WSIs were processed by a multi-instance deep learning model to obtain the patient-level survival risk scores; mRNA expression data were processed by weighted gene co-expression network analysis (WGCNA), and the top hub genes of each module were extracted as risk factors. Information from two modalities was integrated by Cox proportional hazard model to predict patient outcomes. The overall survival predictions of the multi-modality model (Concordance index (C-index): 0.746, 95% confidence interval (CI): +/- 0.077) outperformed these based on histopathology risk score or hub genes, respectively. Furthermore, in the prediction of 1-year and 3-year survival, the area under curve of the model achieved 0.816 and 0.810. In conclusion, this paper provides an effective workflow for multi-modality prognosis of HCC, the integration of histopathology and genomic information has the potential to assist clinical prognosis management.