Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression
Journal Title
Nature Biotechnology
Publication Type
epub ahead of print
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.
Publisher
NPG
WEHI Research Division(s)
Bioinformatics
PubMed ID
35697807
Open Access at Publisher's Site
https://doi.org/10.1038/s41587-022-01342-x
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2022-06-17 09:28:42
Last Modified: 2022-06-17 09:43:41
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