Application of a Glycoproteomics-Based Biomarker Development Method: Alteration in Glycan Structure on Colony Stimulating Factor 1 Receptor as a Possible Glycobiomarker Candidate for Evaluation of Liver Cirrhosis

摘要

The importance of diagnosis and therapies for liver cirrhosis (LC) is indisputable. Thus, a reliable method for monitoring the progression of liver fibrosis and resultant LC is urgently needed. Previously, using a lectin-assisted glycoproteomic method, we identified 26 serum glycoproteins as promising glycobiomarker candidates for monitoring the progression of liver diseases. In this study, we identified colony stimulating factor 1 receptor (CSF1R) as a promising LC marker candidate and then established Wisteria f loribunda agglutinin (WFA)-reactive CSF1R (WFA~+-CSF1R) as a novel possible glycobiomarker candidate by utilizing a glycoproteomics- based strategy. The serum level of WFA+-CSF1R in patients with hepatitis C virus (HCV)-infected liver disease was measured by an antibody-lectin sandwich ELISA. In a proof-ofconcept experiment of the strategy preceding to future clinical studies, LC patients showed a high serum WFA~+-CSF1R level in selected samples (P = 1.3 × 10~(?17)). This result suggests WFA+-CSF1R is a possible biomarker candidate for evaluation of LC. Our results verified feasibility of this strategy for glycobiomarker development.