Isomer-specific profiling of N-glycans derived from human serum for potential biomarker discovery in pancreatic cancer

Yufei Liu; Chang Wang; Ran Wang; Yike Wu; Liang Zhang; Bi-Feng Liu; Liming Cheng; Xin Liu

doi:10.1016/j.jprot.2018.04.016

Isomer-specific profiling of N-glycans derived from human serum for potential biomarker discovery in pancreatic cancer

J Proteomics. 2018 Jun 15:181:160-169. doi: 10.1016/j.jprot.2018.04.016. Epub 2018 Apr 16.

Authors

Yufei Liu¹, Chang Wang¹, Ran Wang¹, Yike Wu¹, Liang Zhang¹, Bi-Feng Liu¹, Liming Cheng², Xin Liu³

Affiliations

¹ The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
² Department of Laboratory Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: chengliming2002@163.com.
³ The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China. Electronic address: xliu@mail.hust.edu.cn.

PMID: 29674015
DOI: 10.1016/j.jprot.2018.04.016

Abstract

Glycosylation is one of the most important post-translational modifications of protein. Recently, global profiling of human serum glycomics has become a noninvasive method for cancer-related biomarker discovery and many studies have focused on compositional glycan profiling. In contrast, structure-specific glycan profiling may provide more potential biomarkers with higher specificity than compositional profiling. In this work, N-glycans released from human serum were neutralized with methylamine and reduced by ammonia-borane complex prior to profiling using nanoLC-ESI-MS with porous graphitized carbon (PGC) and relative abundances of over 280 isomers were compared between pancreatic cancer (PC) cases (n = 32) and healthy controls (n = 32). Statistical analysis identified 25 specific-isomeric biomarkers with significant differences (p-value < 0.05). ROC and PCA analysis were performed to assess the potential biomarkers which were identified as being significantly altered in cancer. The AUCs of the significantly changed specific-isomers were ranging from 0.712 to 0.949. In addition, with the combination of all potential biomarkers, a higher AUC of 0.976 with sensitivity (93.5%) and specificity (90.6%) was obtained. Overall, the proposed strategy coupled to relative quantitative analysis of isomeric glycans make it possible to discover new biomarkers for the diagnosis of PC.

Significance: Pancreatic cancer (PC) has a poor prognosis with a five-year survival rate <5%. Therefore, a strategy for accurate diagnosis of PC is indeed required. In this paper, a dual-derivatized strategy for structure-specific glycan profiling has been used and according to our best knowledge, this is the first application of this strategy for PC biomarker discovery, in which the separation, identification and relative quantification of isomeric glycans can be simultaneously obtained. In addition, by in-depth analysis of isomeric glycans, the full description of the stereo- and region- diversity of glycans can also be achieved, which might provide more potential information for PC biomarker discovery.

Keywords: N-glycans; PC; Potential biomarker; Specific-isomer.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / blood*
Disease-Free Survival
Female
Glycomics*
Glycosylation
Humans
Isomerism
Male
Pancreatic Neoplasms / blood*
Pancreatic Neoplasms / mortality
Polysaccharides / blood*
Survival Rate

Substances

Biomarkers, Tumor
Polysaccharides