biostudies-literatureLi JNational Natural Science Foundation of ChinaChina Postdoctoral Science FoundationNational Key Research and Development Program of China2135-2152https://www.ebi.ac.uk/biostudies/studies/S-EPMC9168967biostudies-literatureUnknown16(11)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 1235 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 bi-anMolecular oncologyPrecision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma.PMC916896791853123817731802019TQ02602019M6637982170512781800655321011922019YFA09005200Dang LLi JShen JMa CSun SMu FZhao THu LZhu BLiu DJia LfalsePrecision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma.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 1235 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 bi-an2022-01-01T00:00:00Z2022 Jun2025-04-03T22:37:29.212Z2025-04-03T22:37:29.212ZS-EPMC91689673485528310.1002/1878-0261.13147