A core fucosylation–derived signature reveals extracellular matrix remodeling and predicts poor outcomes in pancreatic ductal adenocarcinoma

Core fucosylated (CF) glycoproteins are closely associated with the pathogenesis of pancreatic ductal adenocarcinoma (PDAC). However, how core fucosylation alterations connect to critical signaling pathways in PDAC, such as dense extracellular matrix (ECM) remodeling and KRAS–MAPK signaling, remains largely unknown. Here, we re-analyzed core fucosylation profiles of six matched PDAC tumor and adjacent normal tissues from a published dataset and identified 54 significantly up-regulated core fucosylation events, which were predominantly associated with ECM remodeling. Leveraging these events, we developed a PDAC prognostic signature comprising three CF glycoproteins, including LRP1, FN1, and LAMC2. This signature was further validated using the tumor-normal comparison in Clinical Proteomic Tumor Analysis Consortium (CPTAC) PDAC cohort. Then, unbiased screening across 1,387 pathways using the Cancer Genome Atlas Program Pancreatic Adenocarcinoma Database (TCGA-PAAD) identified cell–ECM interactions as the dominant association with the signature. Moreover, it was confirmed using tumor-normal comparison across three independent Gene Expression Omnibus (GEO) cohorts (AUC 0.888–0.941) and was associated with adverse prognosis in TCGA-PAAD. Together, these works proposed a core fucosylation-derived prognostic signature linking glycosylation alterations to matrix remodeling and poor outcome in PDAC.