Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression.

Humans Neoplasms / genetics Genetic Heterogeneity Genomics RNA, Messenger / genetics Disease Progression

Journal

Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648

Informations de publication

Date de publication:
11 2022
Historique:
received: 07 06 2021
accepted: 29 04 2022
pubmed: 14 6 2022
medline: 15 11 2022
entrez: 13 6 2022
Statut: ppublish

Résumé

Single-cell RNA sequencing studies have suggested that total mRNA content correlates with tumor phenotypes. Technical and analytical challenges, however, have so far impeded at-scale pan-cancer examination of total mRNA content. Here we present a method to quantify tumor-specific total mRNA expression (TmS) from bulk sequencing data, taking into account tumor transcript proportion, purity and ploidy, which are estimated through transcriptomic/genomic deconvolution. We estimate and validate TmS in 6,590 patient tumors across 15 cancer types, identifying significant inter-tumor variability. Across cancers, high TmS is associated with increased risk of disease progression and death. TmS is influenced by cancer-specific patterns of gene alteration and intra-tumor genetic heterogeneity as well as by pan-cancer trends in metabolic dysregulation. Taken together, our results indicate that measuring cell-type-specific total mRNA expression in tumor cells predicts tumor phenotypes and clinical outcomes.

Identifiants

DOI: 10.1038/s41587-022-01342-x PMID: 35697807 PMC: PMC9646498
pubmed: 35697807
doi: 10.1038/s41587-022-01342-x
pii: 10.1038/s41587-022-01342-x
pmc: PMC9646498
doi:

Substances chimiques

RNA, Messenger 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1624-1633

Subventions

Organisme : NCI NIH HHS
ID : U01 CA196403
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA224044
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA268380
Pays : United States
Organisme : Department of Health
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC001169
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C416/A21999
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA231465
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA256780
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA183793
Pays : United States
Organisme : Medical Research Council
ID : FC001202
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U01 CA200468
Pays : United States
Organisme : Wellcome Trust
ID : FC001202
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA234629
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA214194
Pays : United States
Organisme : Cancer Research UK
ID : FC001202
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P50 CA221707
Pays : United States
Organisme : Cancer Research UK
ID : C11496/A17786
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : L30 CA171000
Pays : United States
Organisme : Wellcome Trust
ID : FC001169
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC001169
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U24 CA248265
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA239342
Pays : United States
Organisme : Medical Research Council
ID : MR/L016311/1
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : K22 CA234406
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016042
Pays : United States
Organisme : Cancer Research UK
ID : C11496/A30025
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U24 CA224020
Pays : United States

Informations de copyright

© 2022. The Author(s).

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Auteurs

Shaolong Cao (S)

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Jennifer R Wang (JR)

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Shuangxi Ji (S)

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Peng Yang (P)

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Statistics, Rice University, Houston, TX, USA.
ORCID: 0000-0002-0630-9506

Yaoyi Dai (Y)

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Baylor College of Medicine, Houston, TX, USA.

Shuai Guo (S)

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Matthew D Montierth (MD)

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Baylor College of Medicine, Houston, TX, USA.
ORCID: 0000-0002-0860-1420

John Paul Shen (JP)

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Xiao Zhao (X)

Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Jingxiao Chen (J)

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Jaewon James Lee (JJ)

Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Paola A Guerrero (PA)

Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Nicholas Spetsieris (N)

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Nikolai Engedal (N)

Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
ORCID: 0000-0003-3718-3464

Sinja Taavitsainen (S)

Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland.
ORCID: 0000-0001-7559-9853

Kaixian Yu (K)

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Julie Livingstone (J)

Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA.
Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA.
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
ORCID: 0000-0002-8424-3768

Vinayak Bhandari (V)

Department of Medical Biophysics, University of Toronto, Toronto ON, Canada.
ORCID: 0000-0003-0265-0835

Shawna M Hubert (SM)

Department of Thoracic Head Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-7907-9609

Najat C Daw (NC)

Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-6941-8005

P Andrew Futreal (PA)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0001-8663-2671

Eleni Efstathiou (E)

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Bora Lim (B)

Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-4182-6058

Andrea Viale (A)

Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Jianjun Zhang (J)

Department of Thoracic Head Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0001-7872-3477

Matti Nykter (M)

Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland.
ORCID: 0000-0001-6956-2843

Bogdan A Czerniak (BA)

Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Powel H Brown (PH)

Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-3398-163X

Charles Swanton (C)

The Francis Crick Institute, London, UK.
ORCID: 0000-0002-4299-3018

Pavlos Msaouel (P)

Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Anirban Maitra (A)

Sheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0001-7923-9978

Scott Kopetz (S)

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0001-9647-3416

Peter Campbell (P)

Cancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.
ORCID: 0000-0002-3921-0510

Terence P Speed (TP)

Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VC, Australia.
School of Mathematics and Statistics, The University of Melbourne, Melbourne, VC, Australia.
ORCID: 0000-0002-5403-7998

Paul C Boutros (PC)

Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA.
Institute for Precision Health, University of California, Los Angeles, Los Angeles, CA, USA.
Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Medical Biophysics, University of Toronto, Toronto ON, Canada.
ORCID: 0000-0003-0553-7520

Hongtu Zhu (H)

Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0002-6781-2690

Alfonso Urbanucci (A)

Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.

Jonas Demeulemeester (J)

Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.
Department of Human Genetics, KU Leuven, Leuven, Belgium.

Peter Van Loo (P)

Cancer Genomics Laboratory, The Francis Crick Institute, London, UK.
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
ORCID: 0000-0003-0292-1949

Wenyi Wang (W)

Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. wwang7@mdanderson.org.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. wwang7@mdanderson.org.
ORCID: 0000-0003-0617-9438

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Estimation of tumor cell total mRNA expression...
questionsmedicales.fr › Tumeurs › Estimation of tumor cell total mRNA expression...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Hétérogénéité génétique › Estimation of tumor cell total mRNA expression...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Estimation of tumor cell total mRNA expression...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Estimation of tumor cell total mRNA expression...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Évolution de la maladie › Estimation of tumor cell total mRNA expression...