Large-scale serum N-glycomics tracks N-glycosylation dynamics in hepatocellular carcinoma progression and enables early diagnosis

作者：Bin Fu, Jierong Chen, Xuejiao Liu, Jiale Li, Xisong Feng, Jun Wang, Ye Li, Yuxiao Zhang, Yuxiao Zhang, Jianhong Ma, Yunxia Wang, Bing Gu, Ying Zhang, Ying Zhang, Haojie Lu · 发表于：Nature Communications · 年份：2026 · DOI：10.1038/s41467-026-68579-x · 被引用次数：9 · 研究领域：Glycosylation and Glycoproteins Research、Galectins and Cancer Biology、Infant Nutrition and Health

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, yet the role of N-glycosylation in its pathogenesis remains unclear. We applied a multi-center, large-cohort N-glycomics strategy combining isomer-specific glycan profiling with multi-omics integration to characterize disease-associated glycan alterations and develop serum-based diagnostic models. Serum N-glycomes from 1,074 individuals across health, chronic hepatitis B, cirrhosis, and HCC were analyzed using a high-throughput pipeline of N-glycan release, derivatization, enrichment, and mass spectrometry. HCC progression was marked by pronounced increases in branching and fucosylation, elevated bisecting GlcNAc, and reduced galactosylation. Machine learning models built on these glycan signatures achieved high diagnostic accuracy (AUC 0.84-0.93), significantly outperforming alpha-fetoprotein, with performance validated in two external cohorts. Integrative glycoproteomic and transcriptomic analyses further illuminated the regulatory pathways driving these glycan shifts, highlighting N-glycosylation as a promising axis for mechanistic insight and early HCC detection.