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Serum N ‐glycans outperform CA19‐9 in diagnosis of extrahepatic cholangiocarcinoma
Author(s) -
Wang Mengmeng,
Fang Meng,
Zhu Jianhui,
Feng Huijuan,
Warner Elisa,
Yi Changhong,
Ji Jun,
Gu Xing,
Gao Chunfang
Publication year - 2017
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.201700084
Subject(s) - glycome , glycan , glycomics , computational biology , glycoprotein , glycosylation , biology , chemistry , microbiology and biotechnology , biochemistry
Extensive efforts have been devoted to improve the diagnosis of extrahepatic cholangiocarcinoma (ECCA) due to its silent clinical character and lack of effective diagnostic biomarkers. Specific alterations in N ‐glycosylation of glycoproteins are considered a key component in cancer progression, which can serve as a distinct molecular signature for cancer detection. This study aims to find potential serum N ‐glycan markers for ECCA. In total, 255 serum samples from patients with ECCA ( n = 106), benign bile tract disease (BBD, n = 60) and healthy controls (HC, n = 89) were recruited. Only 2 μL of serum from individual patients was used in this assay where the N ‐glycome of serum glycoproteins was profiled by DNA sequencer‐assisted fluorophore‐assisted capillary electrophoresis (DSA‐FACE) technology. Multi‐parameter models were constructed by combining the N ‐glycans and carbohydrate antigen 19‐9 (CA19‐9) which is currently used clinically. Quantitative analyses showed that among 13 N ‐glycan structures, the bifucosylated triantennary N ‐glycan (peak10, NA3F2) presented the best diagnostic performance for distinguishing ECCA from BBD and HC. Two diagnostic models (Glycotest1 and Glycotest2) performed better than single N ‐glycan or CA19‐9. Additionally, two N ‐glycan structures (peak9, NA3Fb; peak12, NA4Fb) were tightly related to lymph node metastasis in ECCA patients. In conclusion, sera of ECCA showed relatively specific N ‐glycome profiling patterns. Serum N ‐glycan markers and models are novel, valuable and noninvasive alternatives in ECCA diagnosis and progression monitoring.