Prediction of colorectal cancer diagnosis based on circulating plasma proteins

• Published in: EMBO molecular medicine Vol. 7; no. 9; pp. 1166 - 1178
• Main Authors: Surinova, Silvia, Choi, Meena, Tao, Sha, Schüffler, Peter J, Chang, Ching‐Yun, Clough, Timothy, Vysloužil, Kamil, Khoylou, Marta, Srovnal, Josef, Liu, Yansheng, Matondo, Mariette, Hüttenhain, Ruth, Weisser, Hendrik, Buhmann, Joachim M, Hajdúch, Marián, Brenner, Hermann, Vitek, Olga, Aebersold, Ruedi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.09.2015; EMBO Press; Wiley Open Access; John Wiley & Sons, Ltd; Springer Nature
• Subjects: Accuracy; Biomarkers; Biomarkers, Tumor - blood; Cancer; Candidates; Cell surface; Cellular Biology; Clinical Laboratory Techniques - methods; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Datasets; diagnostic protein biomarker; Diagnostic tests; discovery‐driven and targeted proteomics; EMBO02; EMBO03; EMBO42; Glycoproteins; Humans; Immunoassay; Life Sciences; Mass spectrometry; Mass Spectrometry - methods; Mass spectroscopy; Peptides; Plasma - chemistry; Plasma proteins; Proteins; Proteomics; Research Article; Scientific imaging; Tumors; discovery‐driven and targeted proteomics; diagnostic protein biomarker; colorectal cancer
• ISSN: 1757-4676; 1757-4684
• DOI: 10.15252/emmm.201404873

Non‐invasive detection of colorectal cancer with blood‐based markers is a critical clinical need. Here we describe a phased mass spectrometry‐based approach for the discovery, screening, and validation of circulating protein biomarkers with diagnostic value. Initially, we profiled human primary tumor tissue epithelia and characterized about 300 secreted and cell surface candidate glycoproteins. These candidates were then screened in patient systemic circulation to identify detectable candidates in blood plasma. An 88‐plex targeting method was established to systematically monitor these proteins in two large and independent cohorts of plasma samples, which generated quantitative clinical datasets at an unprecedented scale. The data were deployed to develop and evaluate a five‐protein biomarker signature for colorectal cancer detection. Synopsis A five‐protein biomarker signature discovered and validated by mass spectrometry can accurately predict colorectal cancer (CRC) diagnosis non‐invasively from a blood sample. Secreted protein biomarker candidates discovered in tumor tissue were detected in the circulation of healthy and CRC subjects. A five‐protein predictive diagnostic signature was developed in a cohort of 100 healthy and 100 CRC subjects, and independently validated in an external cohort of 67 healthy and 202 CRC subjects. The protein biomarker signature was found to be more effective for CRC subjects with larger tumors. Graphical Abstract A five‐protein biomarker signature discovered and validated by mass spectrometry can accurately predict colorectal cancer (CRC) diagnosis non‐invasively from a blood sample.