Deep Learning–Based Multi-Omics Integration Robustly Predicts Survival in Liver Cancer

Identifying robust survival subgroups of hepatocellular carcinoma (HCC) will significantly improve patient care. Currently, endeavor of integrating multi-omics data to explicitly predict HCC survival from multiple patient cohorts is lacking. To fill this gap, we present a deep learning (DL)-based model on HCC that robustly differentiates survival subpopulations of patients in six cohorts. We built the DL-based, survival-sensitive model on 360 HCC patients' data using RNA sequencing (RNA-Seq), miRNA sequencing (miRNA-Seq), and methylation data from The Cancer Genome Atlas (TCGA), which predicts prognosis as good as an alternative model where genomics and clinical data are both considered. This DL-based model provides two optimal subgroups of patients with significant survival differences (<i>P</i> = 7.13e-6) and good model fitness [concordance index (C-index) = 0.68]. More aggressive subtype is associated with frequent <i>TP53</i> inactivation mutations, higher expression of stemness markers (<i>KRT19</i> and <i>EPCAM</i>) and tumor marker <i>BIRC5</i>, and activated Wnt and Akt signaling pathways. We validated this multi-omics model on five external datasets of various omics types: LIRI-JP cohort (<i>n</i> = 230, C-index = 0.75), NCI cohort (<i>n</i> = 221, C-index = 0.67), Chinese cohort (<i>n</i> = 166, C-index = 0.69), E-TABM-36 cohort (<i>n</i> = 40, C-index = 0.77), and Hawaiian cohort (<i>n</i> = 27, C-index = 0.82). This is the first study to employ DL to identify multi-omics features linked to the differential survival of patients with HCC. Given its robustness over multiple cohorts, we expect this workflow to be useful at predicting HCC prognosis prediction. <i>Clin Cancer Res; 24(6); 1248-59. ©2017 AACR</i>.