Proximal fluid proteome profiling of mouse colon tumors reveals biomarkers for early diagnosis of human colorectal cancer
Menée à l'aide d'un modèle murin et d'échantillons de sérum prélevés sur des patients présentant des adénomes du côlon-rectum, cette étude suggère que le niveau sérique de la protéine CHI3L1 pourrait être utile pour la détection précoce d'une lésion précancéreuse
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 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;Apc15lox/+ 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 using tandem mass spectrometry. CEA and CHI3L1 human serum protein levels were determined by ELISA. Results: Out of 2172 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 among which 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 to control individuals, in contrast to the CRC biomarker CEA. Conclusions: These data demonstrate that proximal fluid proteome profiling using 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 , résumé, 2012