ArticleNature biotechnology2022
Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression.
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Article in Nature biotechnology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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47 citing papers in PubMed, 74 citations in OpenAlex.
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Authors and funding
40 authors at 8 institutions in 7 countries.
Shaolong Cao *Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jennifer R Wang *Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Shuangxi Ji *Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Peng YangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-0630-9506
Yaoyi DaiDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Shuai GuoDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Matthew D MontierthDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-0860-1420
John Paul ShenDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xiao ZhaoDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jingxiao ChenDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jaewon James LeeSheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Paola A GuerreroSheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nicholas SpetsierisDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nikolai EngedalDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.ORCID http://orcid.org/0000-0003-3718-3464
Sinja TaavitsainenFaculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland.ORCID http://orcid.org/0000-0001-7559-9853
Kaixian YuDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Julie LivingstoneDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-8424-3768
Vinayak BhandariDepartment of Medical Biophysics, University of Toronto, Toronto ON, Canada.ORCID http://orcid.org/0000-0003-0265-0835
Shawna M HubertDepartment of Thoracic Head Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-7907-9609
Najat C DawDepartment of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-6941-8005
P Andrew FutrealDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-8663-2671
Eleni EfstathiouDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Bora LimDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-4182-6058
Andrea VialeDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jianjun ZhangDepartment of Thoracic Head Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7872-3477
Matti NykterFaculty of Medicine and Health Technology, Tampere University and Tays Cancer Center, Tampere, Finland.ORCID http://orcid.org/0000-0001-6956-2843
Bogdan A CzerniakDepartment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Powel H BrownDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-3398-163X
Charles SwantonThe Francis Crick Institute, London, UK.ORCID http://orcid.org/0000-0002-4299-3018
Pavlos MsaouelDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Anirban MaitraSheikh Ahmed Center for Pancreatic Cancer Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-7923-9978
Scott KopetzDepartment of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9647-3416
Peter CampbellCancer Genome Project, Wellcome Trust Sanger Institute, Hinxton, UK.ORCID http://orcid.org/0000-0002-3921-0510
Terence P SpeedBioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VC, Australia.ORCID http://orcid.org/0000-0002-5403-7998
Paul C BoutrosDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-0553-7520
Hongtu ZhuDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-6781-2690
Alfonso UrbanucciDepartment of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Jonas DemeulemeesterCancer Genomics Laboratory, The Francis Crick Institute, London, UK.
Peter Van LooCancer Genomics Laboratory, The Francis Crick Institute, London, UK.ORCID http://orcid.org/0000-0003-0292-1949
Wenyi WangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. wwang7@mdanderson.org.ORCID http://orcid.org/0000-0003-0617-9438
The University of Texas MD Anderson Cancer Center · USOslo University Hospital · NOTampere University Hospital · FIThe Francis Crick Institute · GBUniversity of California, Los Angeles · USThe University of Melbourne · AUUniversity of Toronto · CAWellcome Sanger Institute · GB
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MWomen's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5MTRAINING OF ACADEMIC SURGICAL ONCOLOGISTST32CA009599 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Ashley M Holder, Jennifer A. Wargo · 1988 to 2026
$13.2MProject 3: Inhibiting Oxidative Phosphorylation in Pancreatic CancerP50CA221707 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI KOPETZ, SCOTT, MAITRA, ANIRBAN · 2019 to 2023
$11.0MClinical Validation Center for Early Detection of Pancreatic CancerU01CA200468 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ANIRBAN MAITRA · 2016 to 2026
$11.0MImaging and Molecular Correlates of Progression in Cystic Neoplasms of the PancreasU01CA196403 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MAITRA, ANIRBAN · 2015 to 2020
$5.8MPatient-Derived Models of Prostate Cancer for Personalized MedicineU01CA224044 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHEN, YU, FUTREAL, PHILLIP ANDREW · 2019 to 2023
$5.1MAdvancing method benchmarking and data sharing through crowd-sourced competitions in cancer researchU24CA248265 · NCI · SAGE BIONETWORKS · PI BOUTROS, PAUL CHRISTOPHER, VARMA, SUSHEEL · 2020 to 2024
$4.1MRigorous and reproducible mutational analysis of the urinary exosomal DNAR01CA231465 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DINNEY, COLIN P.N., KALLURI, RAGHU · 2019 to 2023
$3.1MMolecular and immunological heterogeneity of Small Cell Lung Cancer (SCLC) and its impact on relapse and therapeutic responseU01CA256780 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BYERS, LAUREN AVERETT, HEYMACH, JOHN V. · 2021 to 2025
$3.0MPancreatic Ductal Adenocarcinoma Translational Resource Center (PATReC)U24CA224020 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MAITRA, ANIRBAN, SEN, SUBRATA · 2017 to 2021
$2.8MConsistent variable selection in p>>n settingsR01CA158113 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI JOHNSON, VALEN EARL · 2011 to 2020
$2.8MCancer Research UK C11496/A17786Cancer Research UK C11496/A30025Cancer Research UK C416/A21999Cancer Research UK FC001169Cancer Research UK FC001202Department of HealthMedical Research Council FC001169Medical Research Council FC001202Medical Research Council MR/L016311/1NCI NIH HHS K22 CA234406NCI NIH HHS L30 CA171000NCI NIH HHS P30 CA016042NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA221707NCI NIH HHS R01 CA158113NCI NIH HHS R01 CA183793NCI NIH HHS R01 CA231465NCI NIH HHS R01 CA234629NCI NIH HHS R01 CA239342NCI NIH HHS R01 CA268380NCI NIH HHS T32 CA009599NCI NIH HHS U01 CA196403NCI NIH HHS U01 CA200468NCI NIH HHS U01 CA214194NCI NIH HHS U01 CA224044NCI NIH HHS U01 CA256780NCI NIH HHS U24 CA224020NCI NIH HHS U24 CA248265Wellcome Trust FC001169Wellcome Trust FC001202
Abstract
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.
Indexed as
NeoplasmsDisease ProgressionGenetic HeterogeneityGenomicsHumansRNA, MessengerRNA, Messenger
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