Abstract
Background: Colorectal cancer (CRC) comprises a large proportion of malignant tumors, and early detection of CRC is critical for effective treatment and optimal prognosis. We aimed to discover and validate serum autoantibodies for early detection of CRC.Methods: Combined with CRC-associated autoantibodies discovered by serological proteome and multiplex analyses, 26 predefined autoantibodies were evaluated in 315 samples (130 CRCs, 75 advanced adenomas, and 110 healthy controls) by protein microarray analysis. Autoantibodies with potential detection value were verified by enzyme-linked immunosorbent assays (ELISAs). Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the accuracy of the biomarkers.Results: Four serum autoantibodies (ALDH1B1, UQCRC1, CTAG1, and CENPF) showed statistically different levels between patients with advanced neoplasm (CRC or advanced adenoma) and controls in microarray analysis, which were validated by ELISAs. Among the four biomarkers, the ALDH1B1 autoantibody showed the highest detection value with area under the curve (AUC) values of 0.70 and 0.74 to detect CRC and advanced adenoma with sensitivities of 75.68 and 62.31% and specificities of 63.06 and 73.87%, respectively. By combining the four biomarkers, the performance was improved with an AUC of 0.79 to detect CRC and advanced adenomas.Conclusion: The ALDH1B1 autoantibody has a good potential for early detection of CRC and advanced adenoma, and measuring serum autoantibodies against tumor-associated antigens may improve detection of early CRC.
Highlights
Cancer is one of the leading causes of death in the developed world
Using an antigen library of a mixture of total proteins extracted from tumor tissues of six colorectal cancer (CRC) cases, serological proteome analysis (SERPA) analysis was performed to screen CRC-related TAAs
By comparing and matching the antigenic protein profiles of each 2-D immunoblot on the original 2-DE, protein spots that were frequently recognized by CRC serum, but not serum from normal controls, were excised from the gels and subjected to MALDI-TOF-MS analysis
Summary
Cancer is one of the leading causes of death in the developed world. It is estimated that 18.1 million new cancer cases and 9.6 million cancer deaths occurred in 2018, with colorectal cancer (CRC) accounting for 1.8 million new cases and 881,000 deaths [1]. The death rate of CRC was reduced to 52% between 1970 and 2015 [2]. This reduction in mortality is attributed to improvements in treatment (12%), changing patterns in CRC risk factors (35%), and screening uptake (53%) [3]. A study using MALDI-TOF MS combined with magnetic beads identified a panel of serum protein biomarkers, which showed sensitivity and specificity above 85% for all stages of CRC [9], implying the potential value of blood tests of protein markers to detect CRC. Colorectal cancer (CRC) comprises a large proportion of malignant tumors, and early detection of CRC is critical for effective treatment and optimal prognosis. We aimed to discover and validate serum autoantibodies for early detection of CRC
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