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 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.
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Richard A
RA
Moffitt
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Raoud
R
Marayati
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Elizabeth L
EL
Flate
University of North Carolina-Rex Healthcare, Chapel Hill, North Carolina, USA.
Keith E
KE
Volmar
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
S Gabriela Herrera
SG
Loeza
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.|Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
Katherine A
KA
Hoadley
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Naim U
NU
Rashid
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.|Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
Lindsay A
LA
Williams
Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA.
Samuel C
SC
Eaton
Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA.
Alexander H
AH
Chung
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Jadwiga K
JK
Smyla
Eppley Cancer Institute, University of Nebraska, Lincoln, Nebraska, USA.
Judy M
JM
Anderson
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.|Department of Surgery, University of North Carolina, Chapel Hill, North Carolina, USA.
Hong Jin
HJ
Kim
Department of Surgery, Feinberg School of Medicine Northwestern University, Chicago, Illinois, USA.|Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine Northwestern University, Chicago, Illinois, USA.
David J
DJ
Bentrem
Department of Surgery, NorthShore University HealthSystem, Evanston, Illinois, USA.
Mark S
MS
Talamonti
Department of Pathology, David Rubenstein Center for Pancreatic Cancer Research, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Christine A
http://orcid.org/0000-0002-4672-3023
CA
Iacobuzio-Donahue
Eppley Cancer Institute, University of Nebraska, Lincoln, Nebraska, USA.
Michael A
MA
Hollingsworth
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina, USA.|Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina, USA.|Department of Surgery, University of North Carolina, Chapel Hill, North Carolina, USA.
Jen Jen
JJ
Yeh
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D018740:Genetic Heterogeneity; D064593:Heterografts; D006801:Humans; D008297:Male; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D017154:Stromal Cells / Q000473:pathology*