Comprehensive analysis of prognosis markers with molecular features derived from pan-cancer whole-genome sequences

Cancer prognosis markers are useful for treatment decisions; however, the omics-level landscape is not well understood across multiple cancer types. Pan-Cancer Analysis of Whole Genomes (PCAWG) provides unprecedented access to various types of molecular data, ranging from typical DNA mutations and RNA expressions to more deeply analyzed or whole-genomic features, such as HLA haplotypes and structural variations. We analyzed the PCAWG data of 13 cancer types from 1,514 patients to identify prognosis markers belonging to 17 molecular features in the survival analysis based on the Cox and Lasso regression methods. We found that germline features including HLA haplotypes, neoantigens, and the number of structural variations were associated with overall survival; however, mutational signatures were not. Measuring a few markers provided a sufficient prognostic performance evaluated by c-index for each cancer type. DNA markers demonstrated better or comparable prognostic performance compared to RNA markers in some cancer types. "Universal" markers strongly associated with overall survival across cancer types were not identified. These findings will give insights into the clinical implementation of prognosis markers.