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.
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Authors | 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 |
Journal | Nature biotechnology
(Nat Biotechnol)
Vol. 40
Issue 11
Pg. 1624-1633
(11 2022)
ISSN: 1546-1696 [Electronic] United States |
PMID | 35697807
(Publication Type: 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)
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Copyright | © 2022. The Author(s). |
Chemical References |
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Topics |
- Humans
- Neoplasms
(genetics, metabolism)
- Genetic Heterogeneity
- Genomics
- RNA, Messenger
(genetics)
- Disease Progression
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