Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas

Mingming Xu, Zhaoliang Liu, Wenhua Hu, Ying Han, Zhen Wu, Sufeng Chen, Peng Xia, Jing Du, Xumin Zhang, Piliang Hao, Jun Xia*, Shuang Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Original languageEnglish
Pages (from-to)51-64
Number of pages14
JournalJournal of Zhejiang University: Science B
Volume25
Issue number1
DOIs
Publication statusPublished - Jan 2024
Externally publishedYes

Keywords

  • Biomarker
  • Glycoproteomics
  • Glycosylation
  • Mass spectrometry
  • Pancreatic cancer

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