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
Experimental Design: Proximal fluids are a rich source of candidate biomarkers as they contain high
concentrations of tissue-derived proteins. The FabplCre;Apc15lox/þ
mouse model represents early-stage
development of human sporadic CRC. Proximal fluids were collected from normal colon and colon tumors
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 < 0.05) and abundantly (>5-fold) more excreted by tumors than by controls. Further
selection for biomarkers with highest specificity and sensitivity yielded 52 candidates, including S100A9,
MCM4, and four other proteins that have been proposed as candidate biomarkers for human CRC screening
or surveillance, supporting the validity of our approach. For CHI3L1, we verified that protein levels were
significantly increased in sera from patients with adenomas and advanced adenomas compared with control
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.
Clinical Cancer Research 02/2012; 18(20):2613-2624. · 7.74 Impact Factor