Estimation of tumor cell total mRNA expression in 15 cancer types predicts disease progression.


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.

  • 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
PubMed ID
Appears In
Nat Biotechnol, 2022, 40 (11)