Overexpression of O-GlcNAc-transferase associates with aggressiveness of mass-forming cholangiocarcinoma.

O-GlcNAcylation, an important O-linked glycosylation of cellular glycoproteins with a single molecule of N-acetylglucosamine (GlcNAc), is involved in regulation of many cellular processes. Alteration of O-GlcNAcylation is associated with the development and progression of many cancers. Here, we demonstrated aberrant O-GlcNAcylation in the cholangiocarcinoma (CCA) using immunohistochemistry of O-GlcNAc modified proteins (OGP), O-GlcNAc transferase (OGT) and N-acetylglucosaminidase (O-GlcNAcase or OGA). OGP expression was low in normal bile ducts corresponding with the low OGT and high OGA expression. In contrast, OGP was strongly expressed in CCA tissues together with the up-regulation of OGT and down-regulation of OGA. Moreover, elevation of O-GlcNAcylation was associated with non-papillary type CCA and poor survival outcome of CCA patients. Our study showed for the first time that O-GlcNAcylation is increased in CCA tissues and is associated with a poor patient outcome. The OGT expression level could be a useful prognostic indicator and inhibition of O-GlcNAcylation might be a therapeutic target for CCA.