Cited by 2,194Pancreatic and Hepatic Oncology ResearchGene expression and cancer classificationBreast Cancer Treatment Studies

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

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Moffitt, Richard A, Marayati, Raoud, Flate, Elizabeth L, Volmar, Keith E, Loeza, S Gabriela Herrera, Hoadley, Katherine A, Rashid, Naim U, Williams, Lindsay A, Eaton, Samuel C, Chung, Alexander H, Smyla, Jadwiga K, Anderson, Judy M, Kim, Hong Jin, Bentrem, David J, Talamonti, Mark S, Iacobuzio-Donahue, Christine A, Hollingsworth, Michael A, Yeh, Jen Jen·2015·Nature Genetics

DOI 10.1038/ng.3398PMC PMC4912058

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Abstract

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.

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Authors: Moffitt, R. A., Marayati, R., Flate, E. L., Volmar, K. E., Loeza, S. G. H., Hoadley, K. A., Rashid, N. U., Williams, L. A., Eaton, S. C., Chung, A. H., Smyla, J. K., Anderson, J. M., Kim, H. J., Bentrem, D. J., Talamonti, M. S., Iacobuzio-Donahue, C. A., Hollingsworth, M. A., & Yeh, J. J.
Affiliations: University of North Carolina at Chapel Hill (US)
University of Nebraska–Lincoln (US)
Northwestern University (US)
Corresponding author: Yeh, Jen Jen
ORCID: Moffitt, Richard A
Marayati, Raoud
Hoadley, Katherine A
Rashid, Naim U
Williams, Lindsay A
Bentrem, David J
Iacobuzio-Donahue, Christine A
Hollingsworth, Michael A
Yeh, Jen Jen
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2015-09-07
Volume: 47
Issue: 10
Pages: 1168-1178
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng.3398
PMC: PMC4912058
OpenAlex: W1497915798
Cited by: 2,194
References: 63
Citations by year: 2026: 227 · 2025: 237 · 2024: 236 · 2023: 252 · 2022: 256 · 2021: 298 · 2020: 223 · 2019: 168 · 2018: 124 · 2017: 96 · 2016: 65 · 2015: 9
FWCI: 42.80
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (T32CA009156, R01CA140424, P30CA060553)
National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK034897, P30DK034987)
National Institute of Environmental Health Sciences (P30ES010126)
Topics: Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Keywords: pancreatic ductal adenocarcinoma, tumor stroma, tumor subtypes, gene expression signatures, blind source separation, basal-like subtype, prognostic subtypes, metastatic pancreatic cancer, molecular classification
MeSH terms: Adenocarcinoma, Animals, Female, Humans, Male, Pancreatic Neoplasms, Gene Expression, Stromal Cells, Genetic Heterogeneity, Carcinoma, Pancreatic Ductal, Heterografts

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

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