Language

English

Publication Date

7-5-2025

Journal

npj Precision Oncology

DOI

10.1038/s41698-025-01029-x

PMID

40617938

PMCID

PMC12228711

PubMedCentral® Posted Date

7-5-2025

PubMedCentral® Full Text Version

Post-print

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.

Published Open-Access

yes

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