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| IJCEP Copyright © 2007-All rights reserved. |
| International Journal of Clinical and Experimental Pathology |
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 correspondences 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 correspondences 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.