Overexpression of O-GlcNAc-Transferase Associates with Aggressiveness of Mass-Forming Cholangiocarcinoma

Abstract

O-GlcNAcylation, an important O-linked glycosylation of cellular glycoproteins with a single molecule ofN-acetylglucosamine (GlcNAc), is involved in regulation of many cellular processes. Alteration of O-GlcNAcylationis associated with the development and progression of many cancers. Here, we demonstrated aberrantO-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 expressionwas low in normal bile ducts corresponding with the low OGT and high OGA expression. In contrast, OGPwas 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 outcomeof CCA patients. Our study showed for the first time that O-GlcNAcylation is increased in CCA tissues and isassociated with a poor patient outcome. The OGT expression level could be a useful prognostic indicator andinhibition of O-GlcNAcylation might be a therapeutic target for CCA.