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

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival 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 separatio...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912058/
https://www.ncbi.nlm.nih.gov/pubmed/26343385
http://dx.doi.org/10.1038/ng.3398
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author 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
author_facet 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
author_sort Moffitt, Richard A.
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival 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, which includes primary, metastatic, and normal samples. By digitally separating tumor, stroma, and normal gene expression, we have identified and validated two tumor-specific subtypes including a “basal-like” subtype which has worse outcome, and is molecularly similar to basal tumors in bladder and breast cancer. Furthermore, we define “normal” and “activated” stromal subtypes which are independently prognostic. Our results provide new insight 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 is critical.
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spelling pubmed-49120582016-06-17 Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma 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 Nat Genet Article Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival 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, which includes primary, metastatic, and normal samples. By digitally separating tumor, stroma, and normal gene expression, we have identified and validated two tumor-specific subtypes including a “basal-like” subtype which has worse outcome, and is molecularly similar to basal tumors in bladder and breast cancer. Furthermore, we define “normal” and “activated” stromal subtypes which are independently prognostic. Our results provide new insight 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 is critical. 2015-09-07 2015-10 /pmc/articles/PMC4912058/ /pubmed/26343385 http://dx.doi.org/10.1038/ng.3398 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
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
Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma
title Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma
title_full Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma
title_fullStr Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma
title_full_unstemmed Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma
title_short Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma
title_sort virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912058/
https://www.ncbi.nlm.nih.gov/pubmed/26343385
http://dx.doi.org/10.1038/ng.3398
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