Abstract
Molecular correlates of cancer patient overall survival (OS) can provide new insights. Here, we systematically cataloged pan-cancer, multi-omic correlates of OS transcending tumor lineage across 11,019 patients, involving multiple cancer types while correcting for cancer-type-intrinsic OS differences. Significant fractions of genes with mRNA associated with OS in pan-cancer analyses showed concordant associations at the levels of DNA copy number alteration or methylation. Pan-cancer gene signatures of T-cell and macrophage tumor infiltrates were associated with better and worse OS, respectively. Pathways implicated by molecular OS associations included metabolism, PI3K/Akt, Wnt, and TGF-beta receptor. Significant fractions of worse OS-associated genes were essential for cell growth. A pan-cancer RNA signature of aggressive cancers associated with greater sensitivity in vitro to inhibitors of MEK1/2, glycolysis pathway, and HSP90, and with chemotherapy response in patient breast tumors. With therapeutic implications, pan-cancer molecular associations with patient survival reveal genes and pathways underlying more aggressive diseases.