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

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Abstract

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<0.05, 52 differentially expressed intact N-glycopeptides (DEGPs) were found in pancreatic cancer tussues relative to control, where 38 up-regulated and 14 down-regulated, respectively.

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Acknowledgments

This research was financially supported by National Natural Science Foundation of China (21775110, 22074105) and Shanghai Science and Technology Commission (14DZ2261100).

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Correspondence to Zhixin Tian.

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This study was performed in compliance with the Helsinki Declaration on ethical principles for handling human tissue specimens, with all China national regulations and requirements. Written informed consent was obtained from participants. Ethical permission for the study was granted by the ethics committees at Tongji University (Shanghai, China) and Changhai Hospital (Shanghai, China).

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Lu, H., Xiao, K. & Tian, Z. Benchmark of site- and structure-specific quantitative tissue N-glycoproteomics for discovery of potential N-glycoprotein markers: a case study of pancreatic cancer. Glycoconj J 38, 213–231 (2021). https://doi.org/10.1007/s10719-021-09994-8

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