Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer

Abstract

Pancreatic cancer (PC) has a high mortality rate because it is usually diagnosed late. Glycosylation of proteins is known to change in tumor cells during the development of PC. The objectives of this study were to identify and validate the diagnostic value of novel biomarkers based on N-glycomic profiling for PC. In total, 217 individuals including subjects with PC, pancreatitis, and healthy controls were divided randomly into a training group (n = 164) and validation groups (n = 53). Serum N-glycomic profiling was analyzed by DSA-FACE. The diagnostic model was constructed based on N-glycan markers with logistic stepwise regression. The diagnostic performance of the model was assessed further in validation cohort. The level of total core fucose residues was increased significantly in PC. Two diagnostic models designated GlycoPCtest and PCmodel (combining GlycoPCtest and CA19-9) were constructed to differentiate PC from normal. The area under the receiver operating characteristic curve (AUC) of PCmodel was higher than that of CA19-9 (0.925 vs. 0.878). The diagnostic models based on N-glycans are new, valuable, noninvasive alternatives for identifying PC. The diagnostic efficacy is improved by combined GlycoPCtest and CA19-9 for the discrimination of patients with PC from healthy controls.

High-density and targeted glycoproteomic profiling of serum proteins in pancreatic cancer and intraductal papillary mucinous neoplasm

“…The findings of the present study are in agreement with previous studies, reporting improved diagnostic accuracy in discriminating pancreatic cancer by combining N-glycan markers in serum and CA19-9 [25]. The serum N-glycan profile has also been studied in patients with IPMN.…”

Aberrant glycosylation and cancer biomarker discovery: a promising and thorny journey

“…Hepatic Core-fucosylation [18,19] Diagnosis, prognosis CA19-9 (used in clinic) Pancreatic Sialyl-Lewis A structure [20,21] Diagnosis, prognosis Total serum/plasma profiles Hepatic Increased multi-antennary glycans with fucose residues [22] Diagnosis Gastric Decreased core-fucosylated glycans [23,24]; increased hybrid and multi-branched structures and decreased monoantennary, galactose, bisecting type and core fucose structures [25] Diagnosis; monitoring progression Pancreatic Increased core-fucose residues [26] Diagnosis Breast Increased sialylation, branching, and outer-arm fucosylation and decreased high-mannosylated and biantennary core-fucosylated glycans [27] Diagnosis Immunoglobulin G (IgG) Hepatic Decreased galactosylation [28]; increased core-fucosylation [29] Diagnosis; prognosis Colorectal Decreased galactosylation [28]; decreased galactosylation and sialylation; increased core-fucosylation of neutral glycans and decreased core-fucosylation of sialylated glycans [ [35,44] Diagnosis; prognosis Cholangio Increased fucosylation [45] Diagnosis…”

Identifying N-Glycan Biomarkers in Colorectal Cancer by Mass Spectrometry

“…Numerous studies have demonstrated the link between aberrant glycosylation and tumor behavior, by promoting tumor progression, metastasis, and invasion. , Mapping the tumor glycome, along with information on the proteome, will provide a better understanding of disease pathogenesis. Driven by this knowledge and recent technological advances in mass spectrometry (MS)-based glycomics and glycoproteomics, tumor-associated glycans are explored for specific tumor markers and potential therapeutic targets. − …”