切换至 "中华医学电子期刊资源库"

中华胃肠内镜电子杂志 ›› 2025, Vol. 12 ›› Issue (03) : 190 -196. doi: 10.3877/cma.j.issn.2095-7157.2025.03.005

论著

胰腺囊性肿瘤囊液的蛋白质O-糖基化特征分析
程冰倩1,2, 柴宁莉2,(), 杜晨2, 高飞3, 李惠凯2, 冯秀雪2, 赵云云1,2, 令狐恩强2,()   
  1. 1100853 北京,解放军医学院
    2100853 北京,解放军总医院第一医学中心消化内科医学部
    3100034 北京,军委机关事务管理总局
  • 收稿日期:2024-12-09 出版日期:2025-08-15
  • 通信作者: 柴宁莉, 令狐恩强
  • 基金资助:
    北京市自然科学基金(7244302); 解放军总医院青年基金(22QNFC056)

Study of O-glycosylation characteristics in cystic fluid of pancreatic cystic neoplasms

Bingqian Cheng1,2, Ningli Chai2,(), Chen Du2, Fei Gao3, Huikai Li2, Xiuxue Feng2, Yunyun Zhao1,2, Enqiang Linghu2,()   

  1. 1Chinese PLA Medical School, Beijing 100853, China
    2Department of Gastroenterology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
    3Government Offices Administration of The Central Military Commission, Beijing 100034, China
  • Received:2024-12-09 Published:2025-08-15
  • Corresponding author: Ningli Chai, Enqiang Linghu
引用本文:

程冰倩, 柴宁莉, 杜晨, 高飞, 李惠凯, 冯秀雪, 赵云云, 令狐恩强. 胰腺囊性肿瘤囊液的蛋白质O-糖基化特征分析[J/OL]. 中华胃肠内镜电子杂志, 2025, 12(03): 190-196.

Bingqian Cheng, Ningli Chai, Chen Du, Fei Gao, Huikai Li, Xiuxue Feng, Yunyun Zhao, Enqiang Linghu. Study of O-glycosylation characteristics in cystic fluid of pancreatic cystic neoplasms[J/OL]. Chinese Journal of Gastrointestinal Endoscopy(Electronic Edition), 2025, 12(03): 190-196.

目的

探究胰腺囊性肿瘤(PCNs)囊液蛋白质O-糖基化特征,为筛选潜在生物标志物,探索PCNs发生发展机制提供方向。

方法

采用液相色谱串联质谱技术(LC-MS/MS)对胰腺浆液性囊腺瘤(SCN)、黏液性囊性肿瘤(MCN)、导管内乳头状黏液性肿瘤(IPMN)囊液进行完整O-糖肽检测。利用生物信息学方法分析差异糖蛋白功能特征,初步探究PCNs可能的发生发展机制。同时,结合临床数据及目前研究现状,筛选出潜在的生物标志物。

结果

质谱检测和分析结果显示,IPMN与SCN、MCN之间的蛋白O-糖基化差异较大,IPMN与SCN之间存在156个上调、17个下调差异糖肽。IPMN与MCN之间差异上调糖肽145个,下调2个。基因本体(GO)分析和通路分析结果提示差异糖蛋白主要位于细胞外基质、酶原颗粒膜、高尔基体腔、血液微粒等,主要涉及胃肠上皮的维持、炎性反应的负向调节、急性期反应、细胞内铁离子稳态等生物过程。主要涉及的通路包括补体和凝血级联反应、胰腺分泌、IL-17信号通路、神经活性配体-受体相互作用、ECM-受体相互作用、胆固醇代谢等。最终筛选出8种特征糖蛋白。

结论

(1)IPMN、MCN、SCN之间的囊液蛋白O-糖基化水平存在差异;(2)PCNs发生发展机制可能与免疫反应、信号转导、胃肠上皮维持、胰腺分泌等有关;(3)MUC-5AC、MUC-5B、MUC-2、FN、Elastase-3A、Elastase-3B、Alpha-2-M、PL-RP2有望作为鉴别不同类型PCNs的潜在生物标志物。

Objective

To explore the characteristics of O-glycosylation in the cystic fluid of pancreatic cystic neoplasms (PCNs), providing a direction for further exploring new biomarkers and studying the mechanism of PCNs.

Methods

The cystic fluid of serous cystadenoma (SCN), mucinous cystic neoplasm (MCN), and intraductal papillary mucinous neoplasm (IPMN) was detected by liquid chromatography- tandem mass spectrometry (LC-MS/MS). Bioinformatics analysis technology was used to analyze the differential glycoproteins, preliminarily exploring the possible mechanism of PCNs.Meanwhile, combined with clinical data and current research status, the potential biomarkers were explored.

Results

According to the mass spectrometry detection, there were significant differences in protein O-glycosylation between IPMN, SCN, and MCN.A total of 156 up-regulated and 17 down-regulated differential glycopeptides were discovered between IPMN and SCN.Meanwhile, between IPMN and MCN, there were 145 up-regulated glycopeptides and 2 down-regulated.The results of gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that the differential glycoproteins were mainly located in the extracellular matrix, zymogen granule membrane, Golgi cavity, blood microparticles, etc., which were mainly involved in the maintenance of gastrointestinal epithelium, negative regulation of inflammatory response, acute phase response, intracellular iron homeostasis, and other biological processes.The main related pathways include complement and coagulation cascade, pancreatic secretion, IL-17 signaling pathway, neuroactive ligand-receptor interaction, ECM-receptor interaction, cholesterol metabolism etc.Finally, eight characteristic glycoproteins were selected.

Conclusion

(1) There were differences in the O-glycosylation of protein among IPMN, MCN, and SCN; (2) The mechanism of PCNs may be related to immune response, signal transduction, gastrointestinal epithelial maintenance, and pancreatic secretion, etc.; (3) MUC-5AC, MUC-5B, MUC-2, FN, Elastase-3A, Elastase- 3B, Alpha-2-M and PL-RP2 could be used as potential biomarkers to identify different types of PCNs.

表1 FragPipe软件检索参数
表2 患者基线资料[例(%)]
图1 差异O-糖肽数目统计柱状图注:SCN为浆液性囊腺瘤;MCN为黏液性囊性肿瘤;IPMN为导管内乳头状黏液性肿瘤
图2 MCN vs. SCN差异蛋白GO富集三联柱状图
图3 囊液样本糖蛋白KEGG富集分析气泡图
图4 IPMN vs SCN差异糖蛋白相互作用网络示意图
[1]
Chandwani RAllen PJ.Cystic Neoplasms of the Pancreas[J].Annu Rev Med201667(1):45-57.
[2]
Gardner TBPark WGAllen PJ.Diagnosis and Management of Pancreatic Cysts[J].Gastroenterology2024167(3):454-468.
[3]
Farrell JJFernández-del Castillo C.Pancreatic Cystic Neoplasms: Management and Unanswered Questions[J].Gastroenterology2013, 144(6):1303-1315.
[4]
Farrell JJ.Prevalence,Diagnosis and Management of Pancreatic Cystic Neoplasms:Current Status and Future Directions[J].Gut Liver2015, 9(5):571-589.
[5]
Ardeshna DRCao TRodgers B,et al.Recent advances in the diagnostic evaluation of pancreatic cystic lesions[J].World J Gastroenterol, 202228(6):624-634.
[6]
Li SYWang ZJPan CY,et al.Comparative Performance of Endoscopic Ultrasound-Based Techniques in Patients With Pancreatic Cystic Lesions:A Network Meta-Analysis[J].Am J Gastroenterol2023, 118(2):243-255.
[7]
Thomas DRScott NE.Glycoproteomics:growing up fast[J].Curr Opin Struct Biol202168(1):18-25.
[8]
Li JZhao TLi J,et al.Precision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma [J].Mol Oncol202216(11):2135.
[9]
Costa JStreich LPinto S,et al.Exploring Cerebrospinal Fluid IgG N-Glycosylation as Potential Biomarker for Amyotrophic Lateral Sclerosis[J].Mol Neurobiol201956(8):5729-5739.
[10]
Cao ZMaupin KCurnutte B,et al.Specific Glycoforms of MUC5AC and Endorepellin Accurately Distinguish Mucinous from Nonmucinous Pancreatic Cysts[J].Mol Cell Proteomics201312(10): 2724-2734.
[11]
Haab BBPorter AYue T,et al.Glycosylation Variants of Mucins and CEACAMs as Candidate Biomarkers for the Diagnosis of Pancreatic Cystic Neoplasms[J].Ann Surg2010251(5):937-945.
[12]
Cui MHu YZhang Z,et al.Cyst fluid glycoproteins accurately distinguishing malignancies of pancreatic cystic neoplasm[J].Signal Transduct Target Ther20238(1):406-415.
[13]
Nieminen HNummela PSatomaa T,et al.N-glycosylation in non-invasive and invasive intraductal papillary mucinous neoplasm[J].Sci Rep202313(1):13191-13202.
[14]
刘璐瑶,秦洪强,叶明亮.完整糖基化肽段的富集与质谱解析新技术研究进展[J].色谱202139(10):1045-1054.
[15]
孟凡刚,孟雅冰.蛋白质组学与应用[M].北京:化学工业出版社,2022.
[16]
沈百荣,黄健.蛋白质组信息学[M].北京:科学出版社,2023.
[17]
高春芳.糖基化:未来可期的新型疾病标志物[J].中华检验医学杂志202245(4):315-317.
[18]
Wang YSun YFeng J,et al.Glycopatterns and Glycoproteins Changes in MCN and SCN:A Prospective Cohort Study[J].Biomed Res Int20192019:2871289.
[19]
Carrara SCangi MGArcidiacono PG,et al.Mucin Expression Pattern in Pancreatic Diseases:Findings From EUS-Guided Fine-Needle Aspiration Biopsies[J].Am J Gastroenterol2011106(7):1359-1363.
[20]
Kwon RSSimeone DM.The Use of Protein-Based Biomarkers for the Diagnosis of Cystic Tumors of the Pancreas[J].Int J Proteomics, 20112011:1-9.
[21]
Furukawa TKlöppel GVolkan Adsay N,et al.Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: a consensus study[J].Virchows Arch2005447(5):794-799.
[22]
Furukawa THatori TFujita I,et al.Prognostic relevance of morphological types of intraductal papillary mucinous neoplasms of the pancreas[J].Gut201160(4):509-516.
[23]
Dalton CJLemmon CA.Fibronectin: Molecular Structure, Fibrillar Structure and Mechanochemical Signaling[J].Cells202110(9):2443.
[24]
Topalovski MBrekken RA.Matrix control of pancreatic cancer:new insights into fibronectin signaling[J].Cancer Letters2015381(1): 252-258.
[25]
Paulo JAKadiyala VBanks PA,et al.Mass Spectrometry-Based (GeLC-MS/MS) Comparative Proteomic Analysis of Endoscopically (ePFT) Collected Pancreatic and Gastroduodenal Fluids[J].Clin Transl Gastroenterol20123(5):e14-e23.
[26]
Moore PCCortez JTChamberlain CE,et al.Elastase 3B mutation links to familial pancreatitis with diabetes and pancreatic adenocarcinoma [J].J Clin Invest2019129(11):4676-4681.
[27]
Zhu GFang QZhu F,et al.Structure and Function of Pancreatic Lipase-Related Protein 2 and Its Relationship With Pathological States[J].Front Genet202112:693538.
[28]
Cater JHWilson MRWyatt AR.Alpha-2-Macroglobulin,a Hypochlorite-Regulated Chaperone and Immune System Modulator [J].Oxid Med Cell Longev20192019:5410657.
[29]
Tomihari AKiyota MMatsuura A,et al.Alpha 2-macroglobulin acts as a clearance factor in the lysosomal degradation of extracellular misfolded proteins[J].Sci Rep202313(1):4680.
[30]
Jaldín-Fincati JRActis Dato VDíaz NM,et al.Activated α2-Macroglobulin Regulates LRP1 Levels at the Plasma Membrane through the Activation of a Rab10-dependent Exocytic Pathway in Retinal Müller Glial Cells[J].Sci Rep20199(1):13234.
[1] 徐西伯, 陈华, 孙备. 胰腺囊性肿瘤的诊治进展[J/OL]. 中华普外科手术学杂志(电子版), 2020, 14(06): 643-646.
[2] 宁波, 柴宁莉, 李惠凯, 冯秀雪, 杜晨, 李笑, 张晓彬, 赵鑫, 令狐恩强. 基于新评价体系的胰腺囊性肿瘤消融有效性分析[J/OL]. 中华腔镜外科杂志(电子版), 2021, 14(05): 293-297.
[3] 田孝东, 杨尹默. 胰腺囊性肿瘤分型诊治及相关指南解读[J/OL]. 中华肝脏外科手术学电子杂志, 2022, 11(05): 438-442.
[4] 程冰倩, 柴宁莉, 杜晨, 王湛博, 李惠凯, 冯秀雪, 高飞, 令狐恩强. 超声内镜引导下经穿刺针活检钳活检在胰腺囊性肿瘤诊断中的应用[J/OL]. 中华胃肠内镜电子杂志, 2024, 11(03): 147-152.
[5] 令狐恩强. 超声内镜引导下聚桂醇消融术[J/OL]. 中华胃肠内镜电子杂志, 2023, 10(02): 144-144.
[6] 李惠凯. 胰腺囊性肿瘤的超声内镜诊断[J/OL]. 中华胃肠内镜电子杂志, 2022, 09(03): 180-180.
[7] Anthony Yuen-Bun Teoh, DongWan Seo, William Brugge, John Dewitt, Pradermchai Kongkam, Enqiang Linghu, Matthew T. Moyer, Ji Kon Ry, Khek Yu Ho. 国际专家组关于超声内镜引导下胰腺囊性肿瘤消融的立场声明[J/OL]. 中华胃肠内镜电子杂志, 2019, 06(04): 145-158.
阅读次数
全文


摘要


AI


AI小编
你好!我是《中华医学电子期刊资源库》AI小编,有什么可以帮您的吗?