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发表刊物：Molecular Oncology

摘要：Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem. Although ICC is clinically different from HCC, their molecular differences are still largely unclear. In this study, precision N‐glycoproteomic analysis was performed on both ICC and HCC tumors as well as paracancer tissues to investigate their aberrant site‐specific N‐glycosylation. By using our newly developed glycoproteomic methods and novel algorithm, termed ‘StrucGP’, a total of 486 N‐glycan structures attached on 1,235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors. Notably, glycans with uncommon LacdiNAc (GalNAcβ1‐4GlcNAc) structures were distinguished from their isomeric glycans. In addition to several biantennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc‐containing, tri‐antennary, and core‐fucosylated glycans were uniquely increased in ICC. More interestingly, almost all LacdiNAc‐containing N‐glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1‐4 GalNAc transferases in ICC at both mRNA and protein expression levels. The novel N‐glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets and mechanism investigations.

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收录刊物：SCI