Abstract
Colorectal cancer (CRC) is a major cause of cancer mortality. Currently used CRC biomarkers provide insufficient sensitivity and specificity; therefore, novel biomarkers are needed to improve the CRC detection. Label-free quantitative proteomics were used to identify and compare glycoproteins, enriched by wheat germ agglutinin, from plasma of CRC patients and age-matched healthy controls. Among 189 identified glycoproteins, the levels of 7 and 15 glycoproteins were significantly altered in the non-metastatic and metastatic CRC groups, respectively. Protein-protein interaction analysis revealed that they were predominantly involved in immune responses, complement pathways, wound healing and coagulation. Of these, the levels of complement C9 (C9) was increased and fibronectin (FN1) was decreased in both CRC states in comparison to those of the healthy controls. Moreover, their levels detected by immunoblotting were validated in another independent cohort and the results were consistent with in the study cohort. Combination of CEA, a commercial CRC biomarker, with C9 and FN1 showed better diagnostic performance. Interestingly, predominant glycoforms associated with acetylneuraminic acid were obviously detected in alpha-2 macroglobulin, haptoglobin, alpha-1-acid glycoprotein 1, and complement C4-A of CRC patient groups. This glycoproteomic approach provides invaluable information of plasma proteome profiles of CRC patients and identification of CRC biomarker candidates.
Highlights
Colorectal cancer (CRC) ranks as the third most common cancer accounting for over 1.8 million cases per year based on the global cancer statistics of 2018 [1]
To reduce variation which may occur among individual samples, three groups of pooled plasma samples obtained from healthy controls, patients with non-metastatic and metastatic CRC were studied in a discovery phase (Figure 1A)
The selected biomarker candidates were conformed in individual plasma samples in the study cohort (Figure 1B) as well as validated in another cohort (Figure 1C) using immunoblot assay
Summary
Colorectal cancer (CRC) ranks as the third most common cancer accounting for over 1.8 million cases per year based on the global cancer statistics of 2018 [1]. Colonoscopy is a gold standard method for detecting CRC; people tend to avoid undergoing this technique because of its invasiveness [2]. Carcinoembryogenic antigen (CEA) is the only blood-based biomarker approved for the clinical use to monitor CRC recurrence [3]. CEA is not entirely satisfactory for routine clinical analysis in terms of sensitivity and specificity, so that its level may be found to be altered in benign and inflammatory conditions [3,4]. Finding novel specific and sensitive biomarkers from liquid biopsy specimens such as plasma and serum would be an ideal and relatively non-invasive way for CRC screening and detection
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