Pan-cancer, multi-omic correlates of survival transcending tumor lineage across 11,019 patients reveal targets and pathways

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 d...

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Main Authors: Yiqun Zhang, Fengju Chen, Chad J. Creighton
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-01029-x
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author Yiqun Zhang
Fengju Chen
Chad J. Creighton
author_facet Yiqun Zhang
Fengju Chen
Chad J. Creighton
author_sort Yiqun Zhang
collection DOAJ
description 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.
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spelling doaj-art-b1efe9e31a934f398cb4852d347ab7ae2025-08-20T03:37:22ZengNature Portfolionpj Precision Oncology2397-768X2025-07-019111910.1038/s41698-025-01029-xPan-cancer, multi-omic correlates of survival transcending tumor lineage across 11,019 patients reveal targets and pathwaysYiqun Zhang0Fengju Chen1Chad J. Creighton2Dan L. Duncan Comprehensive Cancer Center, Baylor College of MedicineDan L. Duncan Comprehensive Cancer Center, Baylor College of MedicineDan L. Duncan Comprehensive Cancer Center, Baylor College of MedicineAbstract 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.https://doi.org/10.1038/s41698-025-01029-x
spellingShingle Yiqun Zhang
Fengju Chen
Chad J. Creighton
Pan-cancer, multi-omic correlates of survival transcending tumor lineage across 11,019 patients reveal targets and pathways
npj Precision Oncology
title Pan-cancer, multi-omic correlates of survival transcending tumor lineage across 11,019 patients reveal targets and pathways
title_full Pan-cancer, multi-omic correlates of survival transcending tumor lineage across 11,019 patients reveal targets and pathways
title_fullStr Pan-cancer, multi-omic correlates of survival transcending tumor lineage across 11,019 patients reveal targets and pathways
title_full_unstemmed Pan-cancer, multi-omic correlates of survival transcending tumor lineage across 11,019 patients reveal targets and pathways
title_short Pan-cancer, multi-omic correlates of survival transcending tumor lineage across 11,019 patients reveal targets and pathways
title_sort pan cancer multi omic correlates of survival transcending tumor lineage across 11 019 patients reveal targets and pathways
url https://doi.org/10.1038/s41698-025-01029-x
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AT fengjuchen pancancermultiomiccorrelatesofsurvivaltranscendingtumorlineageacross11019patientsrevealtargetsandpathways
AT chadjcreighton pancancermultiomiccorrelatesofsurvivaltranscendingtumorlineageacross11019patientsrevealtargetsandpathways