胰腺癌不同进展期血清外泌体蛋白质组学分析

doi:10.6040/j.issn.1671-7554.0.2022.0169

摘要/Abstract

摘要： 目的筛选健康对照与不同进展期胰腺癌患者的血清外泌体差异蛋白质,绘制差异蛋白质表达图谱,并分析差异蛋白质参与的生物学过程。方法采用非标记定量蛋白质组学进行外泌体蛋白质检测,筛选差异蛋白质并进行生物信息学分析;利用蛋白免疫印迹对与胰腺癌进展相关的蛋白质进行血清学验证。结果在对照组、胰腺癌未转移组和转移组样品中共检测到2 242个蛋白质。通过不同分组差异蛋白质分析,共鉴定出664个差异具有统计学意义的蛋白质,主要参与囊泡介导转运、局灶黏附、细胞外基质(ECM)受体相互作用等信号通路。此外,鉴定到在3组间差异均有统计学意义的蛋白质5个,验证发现富亮氨酸α2糖蛋白1(LRG1)在胰腺癌转移组外泌体中表达量较高。结论对照组、胰腺癌未转移组和转移组间蛋白质表达存在差异,差异蛋白质主要富集于局灶黏附、细胞外基质受体相互作用等信号通路,且在3组间表达均有差异的外泌体蛋白质LRG1可能成为监测胰腺癌进展的血清学标志物。

关键词: 胰腺癌, 外泌体, 蛋白质组学, 生物信息学, 富亮氨酸α2糖蛋白1

Abstract: Objective To screen the differential proteins of serum exosomes in healthy controls and pancreatic cancer patients with different degrees of progression, draw the profile, and analyze their functions and biological processes. Methods Exosomes were quantitatively analyzed with label-free quantitative proteomic analysis technology. The differential proteins were screened and bioinformatic analysis was performed. The proteins associated with pancreatic cancer progression were serologically verified with Western blotting. Results A total of 2 242 proteins were detected in the control, non-metastatic and metastatic pancreatic cancer samples with label-free quantitative proteomic analysis and a total of 664 proteins with statistically significant differences were identified, which were mainly involved in vesicle-mediated transport, focal adhesion and extracellular cortex matrix(ECM)receptor interaction. Moreover, there were 5 proteins with statistically significant differences among the three groups, of which leucine-rich alpha-2-glycoprotein 1(LRG1)was highly expressed in serum exosomes of metastatic pancreatic cancer. Conclusion There are differences in protein expression patterns among healthy controls, non-metastatic and metastatic pancreatic cancer patients, and the differential proteins are mainly enriched in focal adhesion and ECM-receptor interaction and other signaling pathways. LRG1, which is different in all three groups, may be a serological marker for monitoring the progression of pancreatic cancer.

Key words: Pancreatic cancer, Exosome, Proteomics, Bioinformatics, Leucine-rich alpha-2-glycoprotein 1

中图分类号:

R735.9

李雁儒,李娟,李培龙,杜鲁涛,王传新. 胰腺癌不同进展期血清外泌体蛋白质组学分析[J]. 山东大学学报 (医学版), 2022, 60(10): 33-41.

LI Yanru, LI Juan, LI Peilong, DU Lutao, WANG Chuanxin. Proteomic analysis of serum exosomes in pancreatic cancer with different stages of progress[J]. Journal of Shandong University (Health Sciences), 2022, 60(10): 33-41.

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