Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression
| Autor: | Shaolong Cao, Jennifer R. Wang, Shuangxi Ji, Peng Yang, Yaoyi Dai, Shuai Guo, Matthew D. Montierth, John Paul Shen, Xiao Zhao, Jingxiao Chen, Jaewon James Lee, Paola A. Guerrero, Nicholas Spetsieris, Nikolai Engedal, Sinja Taavitsainen, Kaixian Yu, Julie Livingstone, Vinayak Bhandari, Shawna M. Hubert, Najat C. Daw, P. Andrew Futreal, Eleni Efstathiou, Bora Lim, Andrea Viale, Jianjun Zhang, Matti Nykter, Bogdan A. Czerniak, Powel H. Brown, Charles Swanton, Pavlos Msaouel, Anirban Maitra, Scott Kopetz, Peter Campbell, Terence P. Speed, Paul C. Boutros, Hongtu Zhu, Alfonso Urbanucci, Jonas Demeulemeester, Peter Van Loo, Wenyi Wang |
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| Přispěvatelé: | Tampere University, BioMediTech, TAYS Cancer Centre |
| Rok vydání: | 2022 |
| Předmět: |
3122 Cancers
Messenger Biomedical Engineering Bioengineering Applied Microbiology and Biotechnology Genetic Heterogeneity Signalling & Oncogenes Ecology Evolution & Ethology Neoplasms Genetics Humans 2.1 Biological and endogenous factors RNA Messenger Aetiology Cancer Computational & Systems Biology Chemical Biology & High Throughput Human Biology & Physiology Human Genome Genome Integrity & Repair Genomics Tumour Biology Disease Progression Molecular Medicine RNA Genetics & Genomics Biotechnology |
| Zdroj: | Nature biotechnology, vol 40, iss 11 |
| DOI: | 10.25418/crick.21533457.v1 |
| Popis: | 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. ispartof: NATURE BIOTECHNOLOGY vol:40 issue:11 pages:1624-+ ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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