IDDF2024-ABS-0328 Clinical value of CLU protein as a marker of cancer transformation in intestinal polypitis based on serum proteomic study

<h3>Background</h3> Based on the theory of ‘inflammation-cancer transformation’, the aim of this study was to seek early specific serum biomarkers for colorectal adenomas for early screening and to abort the progression of colorectal polyps to carcinoma from the inflammation-polyp-neoplasia pathway. <h3>Methods</h3> Protein profiles of 17 patients with adenoma/tumor degeneration, 13 patients with inflammation/hyperplasia, and 26 healthy control patients were analyzed by magnetic bead weak cation exchange and matrix-assisted laser desorption ionization time-of-flight mass spectrometry to identify and screen for significantly different peptides. Enzyme-linked immunosorbent assay (ELISA) was used to verify the expression levels of the target proteins. Then, protein immunoblotting was used to verify the expression of the target proteins. Finally, the diagnostic efficacy of the protein was evaluated using the subject’s work characterization curve (ROC), and the threshold value for the best indicator of diagnostic efficacy was determined. <h3>Results</h3> Protein profiling results suggested that the indicators that correlated well with colorectal adenoma progression were Clusterin, CLU, Albumin, ALB and serum Fibrinogen alpha chain, where CLU protein concentration was in the adenoma/tumor group, inflammation/hyperplasia group, healthy control group tended to decrease in a fold gradient, so it was considered as a target protein. We verified from serum samples and tissue samples using ELISA and WB that CLU protein expression tended to decrease in a gradient during polyp progression.ROC curve analysis suggested that the area under the curve (AUC) of CLU was 0.92, suggesting it has a high diagnostic value as a means of distinguishing adenomatous polyps from non-adenomatous polyps. It is worth noting that the diagnosis of adenomatous polyps is more likely when the protein concentration is less than 2895.78 pg/mL. <h3>Conclusions</h3> There were significant differential expression peaks in the serum protein profiles among the 3 groups. CLU protein expression tended to decrease in a gradient in the normal healthy group, inflammation/proliferative group, and adenoma/neoplastic group. And adenomatous polyps were highly suspected when CLU concentration was lower than 2895.78 pg/mL.