Abstract
At the moment, there is no sensitive clinical test for detecting early-stage colorectal cancer (CRC). Target proteomics has enabled high-throughput verification of hundreds of biomarker candidate proteins. Using this technology, we verified 725 previously reported CRC biomarker candidate proteins that are functionally correlated with CRC in extracellular vesicles (EVs) from patients. Of these, 356 proteins were quantified, and 34 peptides (22 proteins) showed significant differences in the serum EVs between healthy controls and CRC patients of two independent cohorts (n = 77 and 84). These peptides were evaluated as single or multiple markers, and four single peptides in annexin family proteins and eight combinations of peptides showed area under the curve > 0.9 for discriminating between healthy controls and CRC patients. The sensitivities of annexins A3, A4, and A11 peptides for detecting early-stage CRC greatly exceed those of carcinoembryonic antigen. These peptides are promising biomarkers for early detection of CRC.
Highlights
Colorectal cancer (CRC) is one of the most frequent cancers in the world and a significant cause of human mortality[1]
A list of colorectal cancer (CRC) biomarker candidate proteins was obtained from a PubMed database of the medical and biological literature
We applied the following inclusion criteria: (1) protein expression had been verified in human CRC tissue or blood by western blot, enzyme-linked immunosorbent assays (ELISA), or immunohistochemistry; (2) the targeted protein was upregulated in cancer; and (3) the molecular function of the targeted protein related to cancer development and progression had been reported or experimentally verified by RNAi or overexpression of the molecule
Summary
Colorectal cancer (CRC) is one of the most frequent cancers in the world and a significant cause of human mortality[1]. In many clinical studies, verification of protein biomarker candidates is performed using antibody-based quantification assays, mainly enzyme-linked immunosorbent assays (ELISA) Because these assay systems are largely dependent on the quality of antibodies, it is difficult to simultaneously evaluate numerous marker candidates. Whiteaker et al performed quantification of a large number of putative breast cancer biomarker candidates using an SRM method in patient plasma[7]. Their strategy demonstrated the usefulness of SRM for biomarker verification and the possibility of its application to other bioresources and diseases. EV proteins are considered to be promising biomarker candidates
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