Benchmark of site- and structure-specific quantitative tissue N-glycoproteomics for discovery of potential N-glycoprotein markers: a case study of pancreatic cancer

• Published in: Glycoconjugate journal 2021-04, Vol.38 (2), p.213-231
• Main Authors: Lu, Haoran, Xiao, Kaijie, Tian, Zhixin
• Format: Article
• Language: English
• Subjects: Antibiotics; Benchmarking; Biochemistry; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Databases, Protein; Gastrointestinal tract; Glycopeptides; Glycoproteins; Glycoproteins - analysis; Glycoproteins - chemistry; Glycoproteins - metabolism; Humans; Isotope Labeling; Life Sciences; Mass Spectrometry and the Analysis of Glycoconjugates; Mass spectroscopy; Monosaccharides; Original Article; Pancreatic cancer; Pancreatic Neoplasms - metabolism; Pathology; Proteomics - methods; Search Engine; Tandem Mass Spectrometry - methods
• ISSN: 0282-0080; 1573-4986
• DOI: 10.1007/s10719-021-09994-8

Pancreatic cancer is a highly malignant tumor of the digestive tract that is difficult to diagnose and treat. It is more common in developed countries and has become one of the main causes of death in some countries and regions. Currently, pancreatic cancer generally has a poor prognosis, partly due to the lack of symptoms in the early stages of pancreatic cancer. Therefore, most cases are diagnosed at advanced stage. With the continuous in-depth research of glycoproteomics in precision medical diagnosis, there have been some reports on quantitative analysis of cancer-related cells, plasma or tissues to find specific biomarkers for targeted therapy. This research is based on the developed complete N-linked glycopeptide database search engine GPSeeker, combined with liquid-mass spectrometry and stable diethyl isotope labeling, providing a benchmark of site- and structure-specific quantitative tissue N-glycoproteomics for discovery of potential N-glycoprotein markers. With spectrum-level FDR ≤1%, 20,038 intact N-Glycopeptides corresponding to 4518 peptide backbones, 228 N-glycan monosaccharide compositions 1026 N-glycan putative structures, 4460 N-glycosites and 3437 intact N-glycoproteins were identified. With the criteria of ≥1.5-fold change and p value