Abstract
Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide. Except for the existing fecal occult blood test, colonoscopy and sigmoidoscopy, no widely accepted in vitro diagnostic methods have been available. To identify potential peptide biomarkers for CRC, serum samples from a discovery cohort (100 CRC patients and 100 healthy controls) and an independent validation cohort (91 CRC patients and 91 healthy controls) were collected. Peptides were fractionated by weak cation exchange magnetic beads (MB-WCX) and analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Five peptides (peaks at m/z 1895.3, 2020.9, 2080.7, 2656.8 and 3238.5) were identified as candidate biomarkers for CRC. A diagnostic panel based on the five peptides can discriminate CRC patients from healthy controls, with an accuracy of 91.8%, sensitivity of 95.6%, and specificity of 87.9% in the validation cohort. Peptide peaks at m/z 1895.3, 2020.9 and 3238.5 were identified as the partial sequences of complement component 4 (C4), complement component 3 (C3) and fibrinogen α chain (FGA), respectively. This study potentiated peptidomic analysis as a promising in vitro diagnostic tool for diagnosis of CRC. The identified peptides suggest the involvement of the C3, C4 and FGA in CRC pathogenesis.
Highlights
Colorectal cancer (CRC) is the 3rd most common cancer among men and the 2nd most frequent cancer among women after breast cancer [1]
A diagnostic panel based on the five peptides can discriminate CRC patients from healthy controls, with an accuracy of 91.8%, sensitivity of 95.6%, and specificity of 87.9% in the validation cohort
Various studies have suggested that serum peptidome is a promising tool for the effective identification of CRC patients [20,21,22,23,24,25,26,27,28,29,30]
Summary
Colorectal cancer (CRC) is the 3rd most common cancer among men (after lung and prostate cancer) and the 2nd most frequent cancer among women after breast cancer [1]. Due to the discomfort or high cost of these screening methods, only 55% of subjects aged 50 to 64 years have undergone a CRC screening test as suggested [5]. An examination of the entire colon by colonoscopy remains the golden standard for CRC screening, but people are hesitant to schedule a colonoscopy examination due to the complicated bowel preparation, associated discomfort, potential complications and high cost [6,7,8,9]. Carcinoembryonic antigen (CEA) has been extensively used as a blood-based marker for CRC prognosis [12], but it cannot be used as a diagnostic marker due to its relatively low specificity [13]. New blood-based tests that are accurate, safe, inexpensive, widely available, and associated with minimum patient discomfort are urgently required for the diagnosis of CRC
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