A Novel Serum Glycobiomarker for Diagnosis and Prognosis of Cholangiocarcinoma Detected by Butea monosperma Agglutinin

Abstract

Plant lectins are widely used in medical glycosciences and glycotechnology. Many lectin-based techniques have been applied for the detection of disease-associated glycans and glycoconjugates. In this study, Butea monosperma agglutinin (BMA), a lectin purified from seeds of the medicinal plant Butea monosperma, was used for the detection of cholangiocarcinoma (CCA)-associated glycans. Expression of BMA-binding N-acetyl galactosamine/galactose (GalNAc/Gal)-associated glycan (BMAG) in CCA tissues was determined using BMA lectin histochemistry; the results showed that BMAG was undetectable in normal bile ducts and drastically increased in preneoplastic bile ducts and CCA. The study in hamsters showed that an increase of BMAG was associated with carcinogenesis of CCA. Using an in-house double BMA sandwich enzyme-linked lectin assay, BMAG was highly detected in the sera of CCA patients. The level of serum BMAG in CCA patients (N = 83) was significantly higher than non-CCA controls (N = 287) and it was applicable for diagnosis of CCA with 55.4% sensitivity, 81.9% specificity, and 76.0% accuracy. A high level of serum BMAG (≥82.5 AU/mL) was associated with unfavorable survival of CCA patients; this information suggested the potential of serum BMAG as a poor prognostic indicator of CCA. In summary, BMAG was aberrantly expressed in preneoplastic bile ducts and CCA, it was also highly detected in patient serum which potentially used as a marker for diagnosis and prognostic prediction of CCA.

O-GlcNAcylation of Keratin 18 coordinates TCA cycle to promote cholangiocarcinoma progression

“…53,54 Glyco-biomarkers such as CA19-9 and CEA are up-regulated in CCA and exhibit diagnostic value. 55,56 Glyco-analytical methodologies including lectin blot, [57][58][59] glycan microarray 60 and glycoproteomic analysis [61][62][63][64] have been utilized to probe the glycobiology in CCA. In addition, abnormal sialylation, [65][66][67][68] fucosylation 69,70 and O-linked Nacetylgalactosamine (GalNAc) modification (O-GalNAcylation) 60,[71][72][73] have also been implicated in prognostic outcome in human cholangiocarcinoma.…”