{"entity":{"id":"paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015","kind":"paper","name":"Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma","aka":[],"tldr":"The 2015 study that computationally separated cancer cells from the surrounding scar tissue in gene expression data and found two tumour types, classical and basal-like, and two kinds of stroma, each of which predicts survival.","summary":"Moffitt and colleagues at the University of North Carolina applied blind source separation to a diverse collection of pancreatic ductal adenocarcinoma gene expression microarray data, including primary tumour, metastatic and normal samples, to digitally separate tumour, stromal and normal expression. They identified and validated two tumour subtypes, including a basal-like subtype with worse outcome that is molecularly similar to basal tumours of bladder and breast cancer, and defined normal and activated stromal subtypes that are independently prognostic. The abstract records the five-year survival of the disease as 4 percent.","asOf":"2026-09-24","links":[{"label":"Nat Genet 2015","url":"https://doi.org/10.1038/ng.3398"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26343385/"}],"tags":["pancreatic-evidence"],"related":["paper-bailey-molecular-subtypes-pancreatic-nature-2016"],"cancers":["pancreatic"],"sections":[],"technologies":["rna-seq"],"targets":[],"drugs":[],"companies":[],"institutions":["unc-lineberger"],"pathways":["tumor-microenvironment","caf-activation-desmoplasia"],"terms":["desmoplasia","desmoplastic-stroma-rich","cancer-associated-fibroblasts"],"trials":[],"people":[],"bottlenecks":["b-tumor-heterogeneity"],"keyPapers":[],"journals":["nature-genetics"],"dependsOn":[],"notes":[],"journal":"Nature Genetics","year":2015,"doi":"10.1038/ng.3398","pmid":"26343385","authors":"Moffitt RA, Marayati R, Flate EL, et al.","paperType":"basic","findings":["Two tumour subtypes, classical and basal-like; basal-like has worse outcome and resembles basal bladder and breast tumours.","Normal and activated stromal subtypes, independently prognostic.","Five-year survival 4 percent at the time of writing."],"whatItMeans":"The classical versus basal-like split, later tied to GATA6 expression and to chemotherapy response, is the subtype scheme most likely to reach the clinic; the stromal subtypes are why the desmoplastic stroma is treated as a partner in the disease rather than inert scar.","caveats":["Microarray data from mixed sources; the subtype is a continuum and tumours can shift under treatment.","No subtype-directed treatment has yet been proven in a randomised trial."]},"route":"/key-papers/paper-moffitt-virtual-microdissection-subtypes-nat-genet-2015/","neighbours":{"paper":[{"id":"paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014","kind":"paper","name":"Depletion of carcinoma-associated fibroblasts and fibrosis induces immunosuppression and accelerates pancreas cancer with reduced survival","route":"/key-papers/paper-ozdemir-caf-depletion-accelerates-pancreatic-cancer-cancer-cell-2014/"},{"id":"paper-bailey-molecular-subtypes-pancreatic-nature-2016","kind":"paper","name":"Genomic analyses identify molecular subtypes of pancreatic cancer","route":"/key-papers/paper-bailey-molecular-subtypes-pancreatic-nature-2016/"}],"cancer":[{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"institution":[{"id":"unc-lineberger","kind":"institution","name":"UNC Lineberger Comprehensive Cancer Center","route":"/institutions/unc-lineberger/"}],"pathway":[{"id":"caf-activation-desmoplasia","kind":"pathway","name":"Fibroblast activation, desmoplasia & matrix stiffness","route":"/pathways/caf-activation-desmoplasia/"},{"id":"tumor-microenvironment","kind":"pathway","name":"Tumour microenvironment (TME)","route":"/pathways/tumor-microenvironment/"}],"term":[{"id":"cancer-associated-fibroblasts","kind":"term","name":"Cancer-associated fibroblasts (CAFs)","route":"/terms/cancer-associated-fibroblasts/"},{"id":"desmoplasia","kind":"term","name":"Desmoplasia (tumour stroma)","route":"/terms/desmoplasia/"},{"id":"desmoplastic-stroma-rich","kind":"term","name":"Stroma-rich and desmoplastic tumours in molecular data","route":"/terms/desmoplastic-stroma-rich/"}],"bottleneck":[{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"journal":[{"id":"nature-genetics","kind":"journal","name":"Nature Genetics","route":"/journals/nature-genetics/"}],"roadmap":[{"id":"pancreatic-roadmap","kind":"roadmap","name":"Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question","route":"/roadmaps/pancreatic-roadmap/"}],"idea":[{"id":"idea-pdac-stromal-reprogramming-not-depletion","kind":"idea","name":"Reprogramme the stroma rather than remove it: second-generation stromal trials with a stromal biomarker and a survival endpoint","route":"/ideas/idea-pdac-stromal-reprogramming-not-depletion/"}]}}