RESUMO
Outcomes from pancreatic ductal adenocarcinoma (PDAC) remain poor and better methods of prognostication and therapeutic approaches are needed. Recent advances in cancer genomics have led to the development of molecular subtypes of PDAC associated with clinical outcomes. Current evidence also suggests that the subtypes have differential response to first-line chemotherapy regimens. PDAC is also characterized by different stroma and immune environments. Further work is needed to confirm the utility of these subtypes to predicting response to different systemic therapies.
Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/diagnóstico , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , PrognósticoRESUMO
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.