Development of M2BPGi: a novel fibrosis serum glyco-biomarker for chronic hepatitis/cirrhosis diagnostics

Abstract

Many proteins in the living body are glycoproteins, which present glycans linked on their surface. Glycan structures reflect the degree of cell differentiation or canceration and are cell specific. These characteristics are advantageous in the development of various disease biomarkers. Glycoprotein-based biomarkers (glyco-biomarkers) are developed by utilizing the specific changes in the glycan structure on a glycoprotein secreted from the diseased cells of interest. Therefore, quantification of the altered glycan structures is the key to developing a new glyco-biomarker. Glycoscience is a relatively new area of molecular science, and recent advancement of glycotechnologies is remarkable. In the author's institute, new glycoscience technologies have been designed to be efficiently utilized for the development of new diagnostic agents. This paper introduces a strategy for glyco-biomarker development, which was successfully applied in the development of Wisteria floribunda agglutinin-positive Mac-2 binding protein M2BPGi, a liver fibrosis marker now commercially available for clinical use.

Association of Mac‐2‐binding protein glycosylation isomer level with nutritional status in chronic liver disease

“…M2BPGi was identified as a novel glycoprotein-based biomarker for staging liver fibrosis in glycoproteomic biomarker screening studies. 14,43 M2BPGi has been reported to have higher efficacy in predicting liver fibrosis than APRI and FIB-4 index in patients with HCV infection. 44 M2BPGi is also a potential marker for hepatocarcinogenesis and for predicting the efficacy of direct-acting antiviral therapy in patients with chronic hepatitis C. 21,45 Figure 3 Associations between liver fibrosis markers and nutritional status markers in all patients.…”

“…Therefore, a novel liver fibrosis marker with higher sensitivity and specificity would be clinically useful. M2BPGi was identified as a novel glycoprotein‐based biomarker for staging liver fibrosis in glycoproteomic biomarker screening studies . M2BPGi has been reported to have higher efficacy in predicting liver fibrosis than APRI and FIB‐4 index in patients with HCV infection .…”

Application of Lectin Microarrays for Biomarker Discovery

“…The M2BPGi assay kit was then established and was validated using more than 8,000 samples. Thus, M2BPGi levels are an excellent diagnostic marker for chronic hepatitis and cirrhosis (Table ) …”

“…Thus, M2BPGi levels are an excellent diagnostic marker for chronic hepatitis and cirrhosis (Table 3). [132] Human inflammatory bowel disease (IBD), Crohn's disease (CD), and ulcerative colitis (UC) are characterized by chronic recurrence and remission of digestive tract inflammation. Significantly higher agalactosyl fraction among fucosylated oligosaccharides of serum IgG was reported in CD and UC patients.…”

Serum M2BPGi level and risk of hepatocellular carcinoma after oral anti‐viral therapy in patients with chronic hepatitis B

“…Mac‐2 binding protein (M2BP) is a glycoprotein involved in intercellular adhesion and interactions with the extracellular matrix . M2BP is widely expressed in various human tissues, but a liver‐specific glycosylation isomer (M2BPGi) can be determined and quantified using the Wisteria floribunda agglutinin immunoassay that is already commercially available in Japan . In the recent years, M2BPGi has emerged as a novel biomarker that correlates well with hepatic fibrosis in patients with chronic liver diseases .…”