Abstract A45: Molecular targets in early detection and differentiation of inflammatory bowel disease-associated colon-rectal-anal cancer disparities

The inflammatory bowel disease (IBD), Crohn9s (CC) and ulcerative colitis (UC), affect approximately 1–2 of every 1000 people in developed countries. These chronic inflammatory diseases result in significant morbidity and mortality. All IBD-associated colorectal-anal cancers (CRAC) occurred in segments of colitis and are frequently diagnosed at an advanced stage. This presentation is a continuation of our work that investigates potential molecules that could define a unique classifier between CC and UC and early detection of CRAC. There are multiple challenges to identifying protein classifiers suggesting outcome prediction and differentiation for patients with IBD and/or IBD-CRAC from molecular interpretation standpoints is complex. While there are technical approach advances, the goal is clear however: to produce scientific evidence which can provide personalized expert care to patients. We have developed an amenable proteomic methodology that supports the diagnostic feasibility to discriminate molecularly, different inflammatory colitis. The histologic layers of colectomy samples from patients with confirmed UC and CC tissues were analyzed using matrix-assisted laser de-sorption/ionization mass spectrometry (MALDI MS) for proteomic profiling. Our previous findings (1) prompted further sample collection resulting in an increased sample size that would allow a more robust analysis. The samples from colon tissues collected in 2008 and samples collected in 2010 were re-randomized into training and independent test sets in order to avoid systematic differences between new and old data sets, typical for MALD-ToF spectra acquired in situ from tissue at different times. MALDI-ToF spectra were included in the analysis only for samples containing more than 3 unique spectra. Our studies have successfully identified 11 highly significant mass-to-charge ratio (m/z) signals (m/z 5045, 6139, 9245, 8413, 3666, 3595, 4122, 8774, 2778, 9232 and 9519) that distinguish CC from UC. These features are independent of the tissue of origin and represent disease specific markers. Some of these signatures were only found in the colonic mucosa (m/z 8413, 3666 & 3595) or submucosa (m/z 4122, 8774, 2778, 9232 & 9519) while others were found in both two layers (m/z 5045, 6139 & 9245). This information may provide new avenues for the development of novel diagnostic, prognostic and therapeutic targets. We will analyze CRAC in IBD segments2,3 to look for these proteins that may help in studying their biological mechanisms in cancer transformation. Support: 3U54CA091408-09S1 (to MMC-VICC Partnership: SE Adunyah & HL Moses) References: 1. M9Koma AE, Seely EH, Washington MK, Schwartz DA, Muldoon RL, Herline AJ, Wise PE, Caprioli RM Proteomic Profiling of Mucosal and Submucosal Colonic Tissues Yields Protein Signatures that Differentiate the Inflammatory Colitides. Inflamm Bowel Dis 2011;17:875-83. 2. M9Koma AE, Moses HL, Adunyah SE. Inflammatory bowel disease-associated colorectal cancer: proctocolectomy andmucosectomy does not necessarily eliminate pouch related cancer incidences. Int J colorect Dis 2011;26:533-52. 3. Um JW, M9Koma AE. Pouch-related dysplasia and adenocarcinoma following restorative proctocolectomy for ulcerative colitis. Tech coloproctol 2011;15:7-16. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A45.