Abstract
Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Early CRC diagnosis is critical, since patients diagnosed at an early stage have an increased five-year survival rate after surgical resection. Serum biomarkers for CRC detection have been described and peptidomic analysis is a promising approach because of its diagnostic potential. A total of 72 CRC patients and 63 healthy controls were investigated. We used a comprehensive peptide analysis technique, BLOTCHIP®-MS analysis, a combination of electrophoresis and mass spectrometry, for high sensitivity detection of trace amounts of serum peptides. The prediction model comprised five peptides: m/z 1616.66 (fibrinogen alpha chain), m/z 2390.26 (alpha-1-antitrypsin), m/z 2858.42 (AHSG S-cysteinylated form), m/z 3622.78 (VASP), and m/z 3949.98 (F. XIIIa). The three CRC groups, stages II to IV, II + IIIa, and IIIb + IV, were discriminated from controls. High diagnostic performance was suggested by AUC (0.924), sensitivity (83%), specificity (92%), and median probability ratio (6.80) to CRC stage II to IV. We describe a prediction model for CRC diagnosis using candidate biomarker peptides discovered by a one-step direct transfer technology (BLOTCHIP®-MS analysis). The high throughput technology has high reproducibility and is applicable for peptide quantification and differential analysis for biomarker discovery.
Highlights
Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality
Data from each peptidome profile was stored in a database, and after completion of the Mass Spectrometry (MS) analysis, batch processing was performed to identify peptides with significantly different concentrations between CRC patients and control groups
In our BLOTCHIP®-MS-based peptidomic analysis of CRC patient sera, 159 peaks were detected in the m/z of 1,500-20,000
Summary
Colorectal cancer (CRC) is one of the most common causes of cancer-related mortality. Since patients diagnosed at stage I have a five-year survival rate of 90–95% after surgical resection, early CRC diagnosis is important [2]. Patients at advanced stages have a five-year survival rate of only 5-10%. The fecal occult blood test (FOBT) and fecal immune test have been clinically accepted as noninvasive diagnostic tests for CRC [3]. Those tests have been reported to provide low sensitivity for CRC detection, especially at an early stage [4]. The development of new screening methods that are highly sensitive, specific, and noninvasive are critical for early diagnosis and timely treatment of CRC
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