Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression
In: Nature Biotechnology, Jg. 40 (2022-11-01), Heft 11
Online
academicJournal
- 1624 - 1633
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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Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression
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Autor/in / Beteiligte Person: | Cao, Shaolong ; Wang, Jennifer R ; Ji, Shuangxi ; Yang, Peng ; Dai, Yaoyi ; Guo, Shuai ; Montierth, Matthew D ; Shen, John Paul ; Zhao, Xiao ; Chen, Jingxiao ; Lee, Jaewon James ; Guerrero, Paola A ; Spetsieris, Nicholas ; Engedal, Nikolai ; Taavitsainen, Sinja ; Yu, Kaixian ; Livingstone, Julie ; Bhandari, Vinayak ; Hubert, Shawna M ; Daw, Najat C ; Futreal, P Andrew ; Efstathiou, Eleni ; Lim, Bora ; Viale, Andrea ; Zhang, Jianjun ; Nykter, Matti ; Czerniak, Bogdan A ; Brown, Powel H ; Swanton, Charles ; Msaouel, Pavlos ; Maitra, Anirban ; Kopetz, Scott ; Campbell, Peter ; Speed, Terence P ; Boutros, Paul C ; Zhu, Hongtu ; Urbanucci, Alfonso ; Demeulemeester, Jonas ; Van Loo, Peter ; Wang, Wenyi |
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Zeitschrift: | Nature Biotechnology, Jg. 40 (2022-11-01), Heft 11 |
Veröffentlichung: | eScholarship, University of California, 2022 |
Medientyp: | academicJournal |
Umfang: | 1624 - 1633 |
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