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

作　　者：Mingming XU Zhaoliang LIU Wenhua HU Ying HAN Zhen WU Sufeng CHEN Peng XIA Jing DU Xumin ZHANG Piliang HAO Jun XIA Shuang YANG 

机构地区：[1]Center for Clinical Mass Spectrometry,College of Pharmaceutical Sciences,Soochow University,Suzhou,215123,China [2]School of Life Science and Technology,ShanghaiTech University,Shanghai,201210,China [3]State Key Laboratory of Genetic Engineering,Department of Biochemistry,School of Life Sciences,Fudan University,Shanghai,200438,China [4]Department of Clinical Laboratory Center,Zhejiang Provincial People’s Hospital,People’s Hospital of Hangzhou Medical College,Hangzhou,310014,China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2024年第1期51-64,共14页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：approved by the Research Ethics Committees of Zhejiang Provincial People’s Hospital(No.QT2022387).

摘　　要：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.

关 键 词：Pancreatic cancer GLYCOSYLATION Biomarker GLYCOPROTEOMICS Mass spectrometry 

分 类 号：R735.9[医药卫生—肿瘤]