Comparative proteomics, network analysis and post-translational modification identification reveal differential profiles of plasma Con A-bound glycoprotein biomarkers in gastric cancer

Yih Huei Uen, Kai Yuan Lin, Ding Ping Sun, Chen Chung Liao, Ming-Song Hsieh, Yung Kai Huang, Yen Wei Chen, Pei Hsuan Huang, Wei Jung Chen, Chih Chun Tai, Kuan Wei Lee, You Chia Chen, Ching Yu Lin

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

In the study, we used Con A affinity chromatography, 1-D gel electrophoresis, and nano-LC-MS/MS to screen biomarker candidates in plasma samples obtained from 30 patients with gastric cancer and 30 healthy volunteers. First, we pooled plasma samples matched by age and sex. We identified 17 differentially expressed Con A-bound glycoproteins, including 10 upregulated proteins and 7 downregulated proteins; these differences were significant (Student's t-test, p-value41, trimethylation at aspartic acid-290, and flavin adenine dinucleotide at histidine-335. Biological significanceOur study was to describe a combinatorial approach of Con A affinity chromatography, 1-D SDS-PAGE, and nano-LC/MS/MS that provides a label-free, comparative glycoproteomic quantification strategy for the investigation of glycoprotein profiles in plasma from gastric cancer patients versus healthy volunteers and to identify glycoprotein biomarkers for the early clinical detection of gastric cancer. Three novel PTMs, HexHexNAc, trimethylation and FAD, in Con A-bound ITIH3 were identified and built in molecular modeling. The aspartic acid-290 trimethylation site was located in a metal ion-dependent adhesion site (MIDAS motif; 290-DXSXS. .T. .D-313) that may influence important function for binding protein ligands.

Original languageEnglish
Pages (from-to)197-213
Number of pages17
JournalJournal of Proteomics
Volume83
DOIs
Publication statusPublished - May 7 2013

Keywords

  • Concanavalin A
  • Gastric cancer
  • Glycoproteins
  • Human plasma
  • Mass spectrometry
  • Post-translational modification

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

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    Uen, Y. H., Lin, K. Y., Sun, D. P., Liao, C. C., Hsieh, M-S., Huang, Y. K., Chen, Y. W., Huang, P. H., Chen, W. J., Tai, C. C., Lee, K. W., Chen, Y. C., & Lin, C. Y. (2013). Comparative proteomics, network analysis and post-translational modification identification reveal differential profiles of plasma Con A-bound glycoprotein biomarkers in gastric cancer. Journal of Proteomics, 83, 197-213. https://doi.org/10.1016/j.jprot.2013.03.007