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Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.1 P.51-64

http://doi.org/10.1631/jzus.B2200652


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


Author(s):  Mingming XU, Zhaoliang LIU, Wenhua HU, Ying HAN, Zhen WU, Sufeng CHEN, Peng XIA, Jing DU, Xumin ZHANG, Piliang HAO, Jun XIA, Shuang YANG

Affiliation(s):  Center for Clinical Mass Spectrometry, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China; more

Corresponding email(s):   yangs2020@suda.edu.cn, andisky_005@126.com

Key Words:  Pancreatic cancer, Glycosylation, Biomarker, Glycoproteomics, Mass spectrometry


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",
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pages="51-64",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2200652"
}

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%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

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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.

胰腺癌细胞和血清完整蛋白质N-糖基化特征的质谱分析

徐明明1,刘兆亮1,胡文华1,韩颖2,吴真3,陈素峰4,夏鹏4,杜璟4,张旭敏3,郝丕良2,夏骏4,杨霜1
1苏州大学药学院临床质谱中心,中国苏州市,215123
2上海科技大学生命科学与技术学院,中国上海市,201210
3复旦大学生命科学学院生物化学系基因工程国家重点实验室,中国上海市,200438
4杭州医学院附属浙江省人民医院临床实验中心,中国杭州市,310014
摘要:胰腺癌作为最恶性的癌症之一,早期干预是提高生存率的关键。目前尚无可靠的方法对其发展为恶性肿瘤进行早期识别,因此在胰腺肿瘤发生过程中发现早期分子变化的要求迫在眉睫。异常糖基化与癌症进展密切相关,对将糖基化变化作为胰腺癌诊断的生物标记物已有较多研究,但详细的糖组学信息,尤其是胰腺癌在药物治疗前后的位点特异性N-糖基化变化研究,仍需进一步深入。本研究采用综合性固相化学酶糖组学手段,对胰腺癌细胞和患者血清中的聚糖、糖基化位点和完整糖肽展开分析。癌症细胞中N-聚糖的分析结果显示,原位肿瘤MIA PaCa-2细胞分泌的糖蛋白增加,然而含有较多分泌糖蛋白的人类血清在其特定糖基化位点上的聚糖却发生了显著变化。上述结果表明,肿瘤特异性糖基化可作为胰腺癌诊断的潜在生物标志物。此外,本研究发现抗KRAS G12C突变的小分子抑制剂AMG-510可显著降低MIA PaCa-2细胞的糖基化水平,这表明KRAS在细胞糖基化过程中发挥抑制作用,将有助于AMG-510的抗肿瘤作用。

关键词:胰腺癌;糖基化;生物标志物;糖蛋白组学;质谱

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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