Journal article
Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression
Nature biotechnology, Vol.40(11), pp.1624-1633
11/01/2022
DOI: 10.1038/s41587-022-01342-x
PMID: 35697807
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.
Total mRNA expression in cancer cells is a marker for disease progression and death.
Details
- Title: Subtitle
- Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression
- Creators
- Shaolong Cao - The University of Texas MD Anderson Cancer CenterJennifer R. Wang - The University of Texas MD Anderson Cancer CenterShuangxi Ji - The University of Texas MD Anderson Cancer CenterPeng Yang - The University of Texas MD Anderson Cancer CenterYaoyi Dai - The University of Texas MD Anderson Cancer CenterShuai Guo - The University of Texas MD Anderson Cancer CenterMatthew D. Montierth - The University of Texas MD Anderson Cancer CenterJohn Paul Shen - The University of Texas MD Anderson Cancer CenterXiao Zhao - The University of Texas MD Anderson Cancer CenterJingxiao Chen - The University of Texas MD Anderson Cancer CenterJaewon James Lee - The University of Texas MD Anderson Cancer CenterPaola A. Guerrero - The University of Texas MD Anderson Cancer CenterNicholas Spetsieris - The University of Texas MD Anderson Cancer CenterNikolai Engedal - Oslo University HospitalSinja Taavitsainen - Tampere UniversityKaixian Yu - The University of Texas MD Anderson Cancer CenterJulie Livingstone - University of California, Los AngelesVinayak Bhandari - University of TorontoShawna M. Hubert - The University of Texas MD Anderson Cancer CenterNajat C. Daw - The University of Texas MD Anderson Cancer CenterP. Andrew Futreal - The University of Texas MD Anderson Cancer CenterEleni Efstathiou - The University of Texas MD Anderson Cancer CenterBora Lim - The University of Texas MD Anderson Cancer CenterAndrea Viale - The University of Texas MD Anderson Cancer CenterJianjun Zhang - The University of Texas MD Anderson Cancer CenterMatti Nykter - University of TampereBogdan A. Czerniak - The University of Texas MD Anderson Cancer CenterPowel H. Brown - The University of Texas MD Anderson Cancer CenterCharles Swanton - The Francis Crick InstitutePavlos Msaouel - The University of Texas MD Anderson Cancer CenterAnirban Maitra - The University of Texas MD Anderson Cancer CenterScott Kopetz - The University of Texas MD Anderson Cancer CenterPeter Campbell - Wellcome Sanger InstituteTerence P. Speed - The University of MelbournePaul C. Boutros - University of TorontoHongtu Zhu - The University of Texas MD Anderson Cancer CenterAlfonso Urbanucci - Oslo University HospitalJonas Demeulemeester - The Francis Crick InstitutePeter Van Loo - The University of Texas MD Anderson Cancer CenterWenyi Wang - The University of Texas MD Anderson Cancer Center
- Resource Type
- Journal article
- Publication Details
- Nature biotechnology, Vol.40(11), pp.1624-1633
- DOI
- 10.1038/s41587-022-01342-x
- PMID
- 35697807
- NLM abbreviation
- Nat Biotechnol
- ISSN
- 1087-0156
- eISSN
- 1546-1696
- Publisher
- Nature Publishing Group US
- Number of pages
- 10
- Grant note
- Norwegian Cancer Society (grant number 198016-2018) Cancer Prevention and Research Institute of Texas as a CPRIT Scholar in Cancer Research and by National Institutes of Health (K22CA234406) the Welch Foundation, MEI Pharma, Inc., Cancer Research United Kingdom (CRUK), Kadoorie Charitable Foundation, NIH/NCI (U01 CA224044-01A1, 1R01CA231465-01A1) NIH (T32CA009599) NIH/NCI under awards number P30CA016042, 1U01CA214194-01 and 1U24CA248265-01 NIH R01CA239342 Norman Jaffe Professorship in Pediatrics Endowment Fund Norman Jaffe Professorship in Pediatrics Endowment Fund, MD Anderson Colorectal Cancer Moon Shot Program, and NIH R01CA183793 American Thyroid Association (American Thyroid Association, lnc.) (https://doi.org/10.13039/100002608) MD Anderson Pancreatic Cancer Moon Shot Program, the Khalifa Bin Zayed Al-Nahyan Foundation, and the National Institutes of Health (NIH U01CA196403, U01CA200468, U24CA224020, P50CA221707)
- Language
- English
- Date published
- 11/01/2022
- Academic Unit
- Surgery
- Record Identifier
- 9985240895902771
Metrics
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