Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma

By Richard A Moffitt, Raoud Marayati, Elizabeth L Flate, Keith E. Volmar, S. G. H. Loeza, Katherine A. Hoadley, N. Rashid, Lindsay A. Williams, Samuel C. Eaton, Alexander H. Chung and 8 more. Nature Genetics, 2015

1,868 citations recorded by the source corpus.

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival rate of 4%. A key hallmark of PDAC is extensive stromal involvement, which makes capturing precise tumor-specific molecular information difficult. Here we have overcome this problem by applying blind source separation to a diverse collection of PDAC gene expression microarray data, including data from primary tumor, metastatic and normal samples. By digitally separating tumor, stromal and normal gene expression, we have identified and validated two tumor subtypes, including a 'basal-like' subtype that has worse outcome and is molecularly similar to basal tumors in bladder and breast cancers. Furthermore, we define 'normal' and 'activated' stromal subtypes, which are independently prognostic. Our results provide new insights into the molecular composition of PDAC, which may be used to tailor therapies or provide decision support in a clinical setting where the choice and timing of therapies are critical.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/99a59fe893c2b2b1e198812998262dbd088891b8

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Citations in the corpus

• Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma (2017, neutral): “mRNA Subtypes Two large studies using either PDAC (Moffitt et al., 2015) or PDAC and other types of pancreatic cancer samples (Bailey et al.”
• Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. (2019, result): “We compared marker genes of the ductal cell subclusters to the classic and basallike gene signatures previously described in PDAC (26).”
• Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives (2021, background): “During the past several years, several subtypes of CAFs in pancreatic ductal adenocarcinoma (PDAC) have been identified through the application of transcriptome analyses, but none of these subtypes was given a specific definition [89, 90].”
• EMT subtype influences epithelial plasticity and mode of cell migration (2018, methodology): “, 2016b), and basal-like (Moffitt et al., 2015)) while P-EMT tumors were associated with well-differentiated transcriptional subtypes (classical/exocrine-like (Collisson et al.”