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Int J Clin Exp Pathol 1(1):32-43;2008
Original Article
Gene Expression Profiles Associated with Advanced Pancreatic Cancer
Domenico Campagna, Leslie Cope, Sindhu S. Lakkur, Clark Henderson, Daniel Laheru and Christine A. Iacobuzio-Donahue
Departments of Pathology, Oncology, and The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Hospital, Baltimore,
Maryland, USA and The Meyerhoff Scholar Program, University of Maryland, Baltimore, Maryland USA
Received 8 July 2007; accepted 15 July 2007; available 1 January 2008
Abstract: Few studies have addressed the expression profiles associated with progression of pancreatic cancer to advanced disease.
Towards this end, we performed expression profiling of a series of normal pancreas, pancreatitis and cancer tissues representing early stage
resected pancreatic cancers (stages pT2/T3), late stage unresectable cancers (stage pT4) and matched metastases to a variety of organ
sites. Microarray data was analyzed using linear modeling of microarray data (LIMMA), and differentially expressed genes were subjected to
Gene Set Enrichment Analysis (GSEA). While robust differences were found in primary cancers as compared to normal pancreatic tissues, no
differences were found between primary cancers and metastases, whether using matched or unmatched samples. When resected pancreatic
cancers were specifically compared to advanced pancreatic cancers, significant differences in gene expression were found associated with
growth at the primary site. These differentially expressed genes were most prominent in gene classes that related to MAPK and Wnt pathway,
metabolism, immune regulation, cell-cell and cell-matrix interactions within the infiltrating carcinoma. One candidate upregulated gene (MXI1)
was validated as having increased expression in advanced stage (T4) carcinomas by real-time PCR (p<0.05) and immunolabeling (p<0.003).
We conclude that in addition to the robust changes in expression that accompany pancreatic carcinogenesis additional specific changes
occur in association with growth at the primary site. By contrast, metastatic spread is not accompanied by reproducible changes in gene
expression. These findings add to our understanding of pancreatic cancer and offer new topics for investigation into the aggressive nature of
this deadly tumor type. (IJCEP707004).
Keywords: c-MYC, MAPK, metastasis, pancreas, oncogene, autopsy
Full Text PDF
Supplementary data: Supplementary tables 1-3
Address all correspondence to: Christine A. Iacobuzio-Donahue, MD, PhD, The Johns Hopkins Hospital, Division of Gastrointestinal/Liver
Pathology, 1550 Orleans Street, CRBII Rm 343, Baltimore, MD 21231. Telephone: 410-955-3511, Fax: 410- 614-0671.
Email:ciacobu@jhmi.edu.
Original Article
Gene Expression Profiles Associated with Advanced Pancreatic Cancer
Domenico Campagna, Leslie Cope, Sindhu S. Lakkur, Clark Henderson, Daniel Laheru and Christine A. Iacobuzio-Donahue
Departments of Pathology, Oncology, and The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins Hospital, Baltimore,
Maryland, USA and The Meyerhoff Scholar Program, University of Maryland, Baltimore, Maryland USA
Received 8 July 2007; accepted 15 July 2007; available 1 January 2008
Abstract: Few studies have addressed the expression profiles associated with progression of pancreatic cancer to advanced disease.
Towards this end, we performed expression profiling of a series of normal pancreas, pancreatitis and cancer tissues representing early stage
resected pancreatic cancers (stages pT2/T3), late stage unresectable cancers (stage pT4) and matched metastases to a variety of organ
sites. Microarray data was analyzed using linear modeling of microarray data (LIMMA), and differentially expressed genes were subjected to
Gene Set Enrichment Analysis (GSEA). While robust differences were found in primary cancers as compared to normal pancreatic tissues, no
differences were found between primary cancers and metastases, whether using matched or unmatched samples. When resected pancreatic
cancers were specifically compared to advanced pancreatic cancers, significant differences in gene expression were found associated with
growth at the primary site. These differentially expressed genes were most prominent in gene classes that related to MAPK and Wnt pathway,
metabolism, immune regulation, cell-cell and cell-matrix interactions within the infiltrating carcinoma. One candidate upregulated gene (MXI1)
was validated as having increased expression in advanced stage (T4) carcinomas by real-time PCR (p<0.05) and immunolabeling (p<0.003).
We conclude that in addition to the robust changes in expression that accompany pancreatic carcinogenesis additional specific changes
occur in association with growth at the primary site. By contrast, metastatic spread is not accompanied by reproducible changes in gene
expression. These findings add to our understanding of pancreatic cancer and offer new topics for investigation into the aggressive nature of
this deadly tumor type. (IJCEP707004).
Keywords: c-MYC, MAPK, metastasis, pancreas, oncogene, autopsy
Full Text PDF
Supplementary data: Supplementary tables 1-3
Address all correspondence to: Christine A. Iacobuzio-Donahue, MD, PhD, The Johns Hopkins Hospital, Division of Gastrointestinal/Liver
Pathology, 1550 Orleans Street, CRBII Rm 343, Baltimore, MD 21231. Telephone: 410-955-3511, Fax: 410- 614-0671.
Email:ciacobu@jhmi.edu.
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