CLC number:
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2024-01-02
Cited: 0
Clicked: 1290
Mingming XU, Zhaoliang LIU, Wenhua HU, Ying HAN, Zhen WU, Sufeng CHEN, Peng XIA, Jing DU, Xumin ZHANG, Piliang HAO, Jun XIA, Shuang YANG. Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas[J]. Journal of Zhejiang University Science B, 2024, 25(1): 51-64.
@article{title="Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas",
author="Mingming XU, Zhaoliang LIU, Wenhua HU, Ying HAN, Zhen WU, Sufeng CHEN, Peng XIA, Jing DU, Xumin ZHANG, Piliang HAO, Jun XIA, Shuang YANG",
journal="Journal of Zhejiang University Science B",
volume="25",
number="1",
pages="51-64",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200652"
}
%0 Journal Article
%T Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas
%A Mingming XU
%A Zhaoliang LIU
%A Wenhua HU
%A Ying HAN
%A Zhen WU
%A Sufeng CHEN
%A Peng XIA
%A Jing DU
%A Xumin ZHANG
%A Piliang HAO
%A Jun XIA
%A Shuang YANG
%J Journal of Zhejiang University SCIENCE B
%V 25
%N 1
%P 51-64
%@ 1673-1581
%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200652
TY - JOUR
T1 - Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas
A1 - Mingming XU
A1 - Zhaoliang LIU
A1 - Wenhua HU
A1 - Ying HAN
A1 - Zhen WU
A1 - Sufeng CHEN
A1 - Peng XIA
A1 - Jing DU
A1 - Xumin ZHANG
A1 - Piliang HAO
A1 - Jun XIA
A1 - Shuang YANG
J0 - Journal of Zhejiang University Science B
VL - 25
IS - 1
SP - 51
EP - 64
%@ 1673-1581
Y1 - 2024
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2200652
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.
[1]Abd-El-HalimYM, el KaoutariA, SilvyF, et al., 2021. A glycosyltransferase gene signature to detect pancreatic ductal adenocarcinoma patients with poor prognosis. eBioMedicine, 71:103541.
[2]Afshar-KharghanV, 2017. The role of the complement system in cancer. J Clin Invest, 127(3):780-789.
[3]ArditoCM, GrünerBM, TakeuchiKK, et al., 2012. EGF receptor is required for KRAS-induced pancreatic tumorigenesis. Cancer Cell, 22(3):304-317.
[4]BassagañasS, CarvalhoS, DiasAM, et al., 2014. Pancreatic cancer cell glycosylation regulates cell adhesion and invasion through the modulation of α2β1 integrin and E-cadherin function. PLoS ONE, 9(5):e98595.
[5]CanonJ, RexK, SaikiAY, et al., 2019. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature, 575(7781):217-223.
[6]CaoLW, LihTM, HuYW, et al., 2022. Characterization of core fucosylation via sequential enzymatic treatments of intact glycopeptides and mass spectrometry analysis. Nat Commun, 13:3910.
[7]CeroniA, MaassK, GeyerH, et al., 2008. GlycoWorkbench: a tool for the computer-assisted annotation of mass spectra of glycans. J Proteome Res, 7(4):1650-1659.
[8]ChenHH, DengZA, HuangCC, et al., 2017. Mass spectrometric profiling reveals association of N-glycan patterns with epithelial ovarian cancer progression. Tumour Biol, 39(7):1010428317716249.
[9]ChenJ, WuW, ChenLJ, et al., 2013. Profiling the potential tumor markers of pancreatic ductal adenocarcinoma using 2D-DIGE and MALDI-TOF-MS: up-regulation of Complement C3 and alpha-2-HS-glycoprotein. Pancreatology, 13(3):290-297.
[10]deLeoz MLA, YoungLJT, AnHJ, et al., 2011. High-mannose glycans are elevated during breast cancer progression. Mol Cell Proteomics, 10(1):M110.002717.
[11]EsmailS, ManolsonMF, 2021. Advances in understanding N-glycosylation structure, function, and regulation in health and disease. Eur J Cell Biol, 100(7-8):151186.
[12]GaoZR, LingXY, ShiCY, et al., 2022. Tumor immune checkpoints and their associated inhibitors. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(10):823-843.
[13]GoldG, GohSK, ChristophiC, et al., 2019. Dilemmas and limitations interpreting carbohydrate antigen 19-9 elevation after curative pancreatic surgery: a case report. Int J Surg Case Rep, 54:20-22.
[14]HolstS, BeloAI, GiovannettiE, et al., 2017. Profiling of different pancreatic cancer cells used as models for metastatic behaviour shows large variation in their N-glycosylation. Sci Rep, 7:16623.
[15]HrubanRH, PetersenGM, HaPK, et al., 1998. Genetics of pancreatic cancer: from genes to families. Surg Oncol Clin North Am, 7(1):1-23.
[16]HuHF, YeZ, QinY, et al., 2021. Mutations in key driver genes of pancreatic cancer: molecularly targeted therapies and other clinical implications. Acta Pharmacol Sin, 42(11):1725-1741.
[17]LeeSJ, EversS, RoederD, et al., 2002. Mannose receptor-mediated regulation of serum glycoprotein homeostasis. Science, 295(5561):1898-1901.
[18]LevinkIJM, KlatteDCF, Hanna-SawiresRG, et al., 2022. Longitudinal changes of serum protein N-Glycan levels for earlier detection of pancreatic cancer in high-risk individuals. Pancreatology, 22(4):497-506.
[19]LiangY, WangW, FangC, et al., 2016. Clinical significance and diagnostic value of serum CEA, CA19-9 and CA72-4 in patients with gastric cancer. Oncotarget, 7(31):49565-49573.
[20]LinYS, TamakoshiA, KikuchiS, et al., 2004. Serum insulin-like growth factor-I, insulin-like growth factor binding protein-3, and the risk of pancreatic cancer death. Int J Cancer, 110(4):584-588.
[21]LiuLY, ZhuB, FangZ, et al., 2021. Automated intact glycopeptide enrichment method facilitating highly reproducible analysis of serum site-specific N-glycoproteome. Anal Chem, 93(20):7473-7480.
[22]LuHR, XiaoKJ, TianZX, 2021. 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(2):213-231.
[23]LumibaoJC, TremblayJR, HsuJ, et al., 2022. Altered glycosylation in pancreatic cancer and beyond. J Exp Med, 219(6):e20211505.
[24]MarrelliD, CarusoS, PedrazzaniC, et al., 2009. CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions. Am J Surg, 198(3):333-339.
[25]MaxwellE, TanY, TanYX, et al., 2012. GlycReSoft: a software package for automated recognition of glycans from LC/MS data. PLoS ONE, 7(9):e45474.
[26]MofidMR, GheysarzadehA, BakhtiyariS, 2020. Insulin-like growth factor binding protein 3 chemosensitizes pancreatic ductal adenocarcinoma through its death receptor. Pancreatology, 20(7):1442-1450.
[27]MunkleyJ, 2019. The glycosylation landscape of pancreatic cancer (Review). Oncol Lett, 17(3):2569-2575.
[28]NarayanasamyA, AhnJM, SungHJ, et al., 2011. Fucosylated glycoproteomic approach to identify a complement component 9 associated with squamous cell lung cancer (SQLC). J Proteomics, 74(12):2948-2958.
[29]NieS, LoA, WuJ, et al., 2014. Glycoprotein biomarker panel for pancreatic cancer discovered by quantitative proteomics analysis. J Proteome Res, 13(4):1873-1884.
[30]PanS, TamuraY, ChenR, et al., 2012. Large-scale quantitative glycoproteomics analysis of site-specific glycosylation occupancy. Mol Biosyst, 8(11):2850-2856.
[31]PanS, ChenR, TamuraY, et al., 2014. Quantitative glycoproteomics analysis reveals changes in N-glycosylation level associated with pancreatic ductal adenocarcinoma. J Proteome Res, 13(3):1293-1306.
[32]ParkHM, HwangMP, KimYW, et al., 2015. Mass spectrometry-based N-linked glycomic profiling as a means for tracking pancreatic cancer metastasis. Carbohydr Res, 413:5-11.
[33]PrestonRJS, RawleyO, GleesonEM, et al., 2013. Elucidating the role of carbohydrate determinants in regulating hemostasis: insights and opportunities. Blood, 121(19):3801-3810.
[34]ReilyC, StewartTJ, RenfrowMB, et al., 2019. Glycosylation in health and disease. Nat Rev Nephrol, 15(6):346-366.
[35]RhoJH, MeadJR, WrightWS, et al., 2014. Discovery of sialyl Lewis A and Lewis X modified protein cancer biomarkers using high density antibody arrays. J Proteomics, 96:291-299.
[36]RoopenianDC, AkileshS, 2007. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol, 7(9):715-725.
[37]RyanDP, HongTS, BardeesyN, 2014. Pancreatic adenocarcin
[38]oma. N Engl J Med, 371(11):1039-1049.
[39]SatoY, FujimotoD, UeharaK, et al., 2016. The prognostic value of serum CA 19-9 for patients with advanced lung adenocarcinoma. BMC Cancer, 16:890.
[40]SethiMK, HancockWS, FanayanS, 2016. Identifying N-glycan biomarkers in colorectal cancer by mass spectrometry. Acc Chem Res, 49(10):2099-2106.
[41]SungH, FerlayJ, SiegelRL, et al., 2021. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 71(3):209-249.
[42]Talar-WojnarowskaR, GasiorowskaA, OlakowskiM, et al., 2011. Clinical value of serum neopterin, tissue polypeptide-specific antigen and CA19-9 levels in differential diagnosis between pancreatic cancer and chronic pancreatitis. Pancreatology, 10(6):689-694.
[43]TaparraK, WangHL, MalekR, et al., 2018. O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis. J Clin Invest, 128(11):4924-4937.
[44]VreekerGCM, Hanna-SawiresRG, MohammedY, et al., 2020. Serum N-Glycome analysis reveals pancreatic cancer disease signatures. Cancer Med, 9(22):8519-8529.
[45]Vukobrat-BijedicZ, Husic-SelimovicA, SoficA, et al., 2013. Cancer antigens (CEA and CA 19-9) as markers of advanced stage of colorectal carcinoma. Med Arch, 67(6):397-401.
[46]XiaoHP, SunFX, SuttapitugsakulS, et al., 2019. Global and site-specific analysis of protein glycosylation in complex biological systems with Mass Spectrometry. Mass Spectrom Rev, 38(4-5):356-379.
[47]XuMM, HuWH, LiuZL, et al., 2021. Glycoproteomic bioanalysis of exosomes by LC‒MS for early diagnosis of pancreatic cancer. Bioanalysis, 13(11):861-864.
[48]XuMM, JinH, WuZ, et al., 2022. Mass spectrometry-based analysis of serum N-glycosylation changes in patients with Parkinson’s disease. ACS Chem Neurosci, 13(12):1719-1726.
[49]YangS, LiY, ShahP, et al., 2013. Glycomic analysis using glycoprotein immobilization for glycan extraction. Anal Chem, 85(11):5555-5561.
[50]YangS, JankowskaE, KosikovaM, et al., 2017. Solid-phase chemical modification for sialic acid linkage analysis: application to glycoproteins of host cells used in influenza virus propagation. Anal Chem, 89(17):9508-9517.
[51]YangS, WuWW, ShenRF, et al., 2018. Identification of sialic acid linkages on intact glycopeptides via differential chemical modification using intactGIG-HILIC. J Am Soc Mass Spectrom, 29(6):1273-1283.
[52]YangS, XiaJ, YangZR, et al., 2021. Lung cancer molecular mutations and abnormal glycosylation as biomarkers for early diagnosis. Cancer Treat Res Commun, 27:100311.
[53]ZhangH, LiXJ, MartinDB, et al., 2003. Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol, 21(6):660-666.
[54]ZhangW, WangYY, DongX, et al., 2021. Elevated serum CA19-9 indicates severe liver inflammation and worse survival after curative resection in hepatitis B-related hepatocellular carcinoma. Biosci Trends, 15(6):397-405.
[55]ZhaoJ, QiuWL, SimeoneDM, et al., 2007. N-linked glycosylation profiling of pancreatic cancer serum using capillary liquid phase separation coupled with mass spectrometric analysis. J Proteome Res, 6(3):1126-1138.
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