Multiscale network modeling reveals the gene regulatory landscape driving cancer prognosis in 32 cancer types

Cancer is a complex disease with diverse molecular mechanisms that affect patient prognosis. Network-based approaches are effective in revealing a holistic picture of cancer prognosis and gene interactions. However, a comprehensive landscape of coexpression networks and prognostic gene modules across multiple cancer types remains elusive. In this study, we performed a systematic analysis of coexpression networks in 32 cancer types. Our analysis identified 4749 prognostic modules that play a vital role in regulating cancer progression. Integrative epigenomic analyses revealed that these modules were regulated by interactions between gene expression and methylation. Coregulated genes of network modules were enriched in chromosome cytobands and preferentially localized in open chromatin regions. The preserved network modules formed 330 module clusters that resided in chromosome hot spots. The cancer-type-specific prognostic modules participated in unique essential biological processes in different cancer types. Overall, our study provides rich resources of prevalent gene networks and underlying multiscale regulatory mechanisms driving cancer prognosis, which lay a foundation for biomarker discovery and therapeutic target development.