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/+) 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.

• Authors: Remond J A Fijneman, Meike de Wit, Maral Pourghiasian, Sander R Piersma, Thang V Pham, Marc O Warmoes, Mehrdad Lavaei, Chloe Piso, Fiona Smit, Pien M Delis-van Diemen, Sietze T van Turenhout, Jochim S Terhaar sive Droste, Chris J J Mulder, Marinus A Blankenstein, Els C Robanus-Maandag, Ron Smits, Riccardo Fodde, Victor W M van Hinsbergh, Gerrit A Meijer, Connie R Jimenez
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 18 Issue 9 Pg. 2613-24 (May 01 2012) ISSN: 1557-3265 [Electronic] United States
• PMID: 22351690 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2012 AACR.

Chemical References

• Adipokines
• Biomarkers, Tumor
• CHI3L1 protein, human
• Carcinoembryonic Antigen
• Chil1 protein, mouse
• Chitinase-3-Like Protein 1
• Glycoproteins
• Lectins
• Proteome

Topics

• Adenoma (diagnosis, metabolism)
• Adipokines (metabolism)
• Animals
• Biomarkers, Tumor (metabolism)
• Carcinoembryonic Antigen (metabolism)
• Case-Control Studies
• Chitinase-3-Like Protein 1
• Chromatography, Liquid
• Colon (metabolism)
• Colorectal Neoplasms (diagnosis, metabolism)
• Early Detection of Cancer
• Enzyme-Linked Immunosorbent Assay
• Female
• Glycoproteins (metabolism)
• Humans
• Lectins (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Precancerous Conditions (diagnosis, metabolism)
• Proteome (analysis)
• Rectum (metabolism)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization