Abstract 5072: Protein signatures associated with dysplasia of ulcerative colitis

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Ulcerative colitis (UC) is an inflammatory bowel disease affecting approximately half a million patients in the United States. Patients with extensive UC of more than eight years duration have an increased risk of colorectal cancer, approximating 0.5-1% per year of colitis. There are major challenges with UC cancer surveillance. Unlike sporadic colon cancer, dysplasia or cancer in UC frequently occurs in benign-appearing colonic mucosa of UC patients without evidence of a polyp. Therefore, an objective molecular biomarker of dysplasia would aid the clinical management of cancer risk in UC patients. We apply a novel, highly sensitive quantitative proteomics approach combining with cutting-edge bioinformatics to develop protein signatures for detecting the neoplastic dysplasia presented in the normal-appearing (i.e., non-dysplastic) colon and rectum for prediction of cancer risk of UC patients. A list of dysregulated proteins potentially associated with colon cancer was identified using large-scale quantitative global protein profiling. Functional analysis was performed to explore the mechanisms that may underlie UC neoplastic progression. Mitochondrial proteins, cytoskeletal proteins, RAS superfamily, proteins relating to apoptosis and metabolism are the important protein groups or pathways differentially expressed in the non-dysplastic and dysplastic tissues of UC progressors, suggesting their importance in UC neoplastic progression. The resultant protein candidates have been ranked and are being rigorously validated using complementary methods, including immunohistochemistry and emerging technology of targeted quantitative proteomics. A molecular signature combining multiple proteins has displayed a statistically significant difference in distinguishing patients with dysplasia/cancer from patients without dysplasia/cancer. Protein biomarker candidates identified in this study may potentially be useful in predictive risk assessment and/or early diagnosis of inflammatory bowel disease associated colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5072. doi:10.1158/1538-7445.AM2011-5072