Alpha Omega Alpha Honor Medical Society

2010 Research Abstract

Differential Gene Expression in Colorectal Cancer Patients with Metabolic Syndrome

Investigator: Abigail Koch, University of South Florida College of Medicine
Mentor: David Shibata, MD, FACS, University of South Florida College of Medicine

Metabolic Syndrome (MetS) as well as its individual components, diabetes, obesity, hypertension and hyperlipidemia are known risk factors for the development of colorectal cancer (CRC). We sought to compare gene expression profiles between CRCs derived from patients with and without MetS. Available tissue resources from patients with previously untreated primary CRC having undergone surgical resection were identified from 2 sources: 1) The Moffitt Cancer Center (MCC) Total Cancer CareTM initiative, a formalized institutional tissue acquisition and gene expression profiling program, from 2005-2009 (Group 1; n=72; 60 MetS-, 12 MetS+) and 2) Archival CRCs profiled at MCC from 1994-2003 (Group 2; n=50; 35 MetS-, 15 Mets+). Microarray analyses were performed using a custom Affymetrix GeneChip (~60,000 probesets, Group 1) and Affymetrix U133 Plus 2.0 GeneChip (~55,000 probesets, Group 2). A Student's t test was used to identify differentially expressed genes and MetaCore GeneGO was used to identify significantly altered biologic pathways. In Group 1, 592 probesets (p<0.01) were differentially expressed in MetS CRCs. By GeneGO pathway analysis, 27 pathways were significantly over-represented. In Group 2, 399 probesets (p<0.01) and 36 pathways (p<0.05) were differentially altered in MetS tumors. Between Groups 1 and 2, a total of 5 genes and 1 pathway demonstrated overlap and were significantly altered. The SLIT/ROBO tumor angiogenesis pathway was upregulated in MetS tumors from both groups. Most notably among individual genes, the PNPLA8 gene was over expressed in MetS+ CRCs from both groups. PNPLA8 has reported effects on insulin resistance, obesity, adipocyte development and CRC tumorigenesis. Across two independent datasets, we have demonstrated that there are distinct molecular alterations that are associated with CRC occurring in patients with MetS. Our findings warrant further investigation with respect to MetS-related CRC tumorigenesis as well as for potential roles as novel therapeutic targets and biomarkers.

Updated on June 8, 2011.

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