Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression.
Abstact
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.
Authors
- Bhandari V
- Boutros PC
- Brown PH
- Campbell P
- Cao S
- Chen J
- Czerniak BA
- Dai Y
- Daw NC
- Demeulemeester J
- Efstathiou E
- Engedal N
- Futreal PA
- Guerrero PA
- Guo S
- Hubert SM
- Ji S
- Kopetz S
- Lee JJ
- Lim B
- Livingstone J
- Maitra A
- Montierth MD
- Msaouel P
- Nykter M
- Shen JP
- Speed TP
- Spetsieris N
- Swanton C
- Taavitsainen S
- Urbanucci A
- Van Loo P
- Viale A
- Wang JR
- Wang W
- Yang P
- Yu K
- Zhang J
- Zhao X
- Zhu H