Su1876 Proximal Fluid Proteome Profiling of Mouse Colon Tumors Reveals Biomarkers for Early Diagnosis of Human Colorectal Cancer

Abstract

Purpose: Early detection of colorectal cancer (CRC) and its precursor lesions is an effective approach to reduce CRC mortality rates. This study aimed to identify novel protein biomarkers for the early diagnosis of CRC. Experimental Design: Proximal fluids are a rich source of candidate biomarkers as they contain high concentrations of tissue-derived proteins. The FabplCre;Apc 15lox/þ mouse model represents early-stage development of human sporadicCRC. Proximalfluids werecollected fromnormalcolon andcolontumors and subjected to in-depth proteome profiling by tandem mass spectrometry. Carcinoembryonic antigen (CEA) and CHI3L1 human serum protein levels were determined by ELISA. Results: Of the 2,172 proteins identified, quantitative comparison revealed 192 proteins that were significantly (P 5-fold) more excreted by tumors than by controls. Further selection for biomarkers with highest specificity and sensitivity yielded 52 candidates, including S100A9, MCM4,andfourotherproteinsthathavebeenproposedascandidatebiomarkersforhumanCRCscreening or surveillance, supporting the validity of our approach. For CHI3L1, we verified that protein levels were significantlyincreasedinserafrompatientswithadenomasandadvancedadenomascomparedwithcontrol individuals, in contrast to the CRC biomarker CEA. Conclusion: These data show that proximal fluid proteome profiling with a mouse tumor model is a powerful approach to identify candidate biomarkers for early diagnosis of human cancer, exemplified by increased CHI3L1 protein levels in sera from patients with CRC precursor lesions. Clin Cancer Res; 18(9); 2613-24. � 2012 AACR.