Abstract 1563: Stool proteomics reveals novel candidate biomarkers for colorectal cancer screening

Abstract

Abstract Introduction and objectives: Early detection of colorectal cancer (CRC) and its precursor lesions is an effective approach to reduce CRC mortality rates. The fecal immunochemical test (FIT) is a non-invasive CRC screening test that detects small traces of the blood protein hemoglobin. Although beneficial in its current form, the FIT test characteristics leave room for improvement. The aim of the present study was to identify and validate novel protein biomarkers in stool that complement or outperform the current hemoglobin-based test, to improve its diagnostic accuracy. Methods: Proteins isolated from stool from 10 subjects without any signs of colorectal neoplasia (controls) at colonoscopy and from 12 CRC patients were analyzed by GeLC-MS/MS (discovery set). Data were analyzed by comparing protein abundancies, measured as spectral counts. Analysis of differential proteins was performed using the beta-binomial test. Findings were validated by mass spectrometry (Q-Exactive) in an independent series of 292 stool samples obtained from control subjects (n = 109) and subjects with adenomas (n = 55), advanced adenomas (n = 53), or CRCs (n = 75). Results and Discussion: In total 830 human proteins were identified in the discovery set, of which 134 were significantly enriched in CRC. These included 78 proteins that were significantly more enriched in FIT-negative CRC stool samples compared to controls. Preliminary analysis of the validation set indicates that more than half of these markers are significantly more abundant in CRC samples compared to controls. Conclusion: Proteome profiling of stool samples revealed novel candidate biomarkers to improve current CRC screening tests. More data analysis is currently ongoing to select most promising protein biomarkers for clinical assay development. Citation Format: Linda JW Bosch, Meike de Wit, Annemieke C. Hiemstra, Sander Piersma, Thang Pham, Gideon Oudgenoeg, George Scheffer, Sandra Mongera, Malgorzata Komor, Jochim Terhaar Sive Droste, Frank A. Oort, Sietze van Turenhout, Ilhame Ben Larbi, Chris JJ Mulder, Beatriz Carvalho, Remond JA Fijneman, Connie Jimenez, Gerrit A. Meijer. Stool proteomics reveals novel candidate biomarkers for colorectal cancer screening. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1563. doi:10.1158/1538-7445.AM2015-1563