胰腺癌患者血清来源的外泌体促进转移：基于iTRAQ的蛋白质组学分析
Serum Derived Exosomes From Pancreatic Cancer Patients Promoted Metastasis: An iTRAQ-Based Proteomic Analysis.
作者信息
Tang Puxian, Tao Lianyuan, Yuan Chunhui, Zhang Lingfu, Xiu Dianrong
机构信息
Department of General Surgery, Peking University Third Hospital, Beijing 100191, People's Republic of China.
Department of Intensive Care Unit, Beijing Hospital, Beijing 100730, People's Republic of China.
出版信息
Onco Targets Ther. 2019 Nov 6;12:9329-9339. doi: 10.2147/OTT.S229494. eCollection 2019.
BACKGROUND
Pancreatic cancer (PC) is one of the most aggressive malignancies and has a poor prognosis despite being extensively researched. The role of serum-derived exosomes in tumorigenesis and the development of PC is still unclear.
METHOD
The present study employed iTRAQ-based proteomic analysis to search for differences between the serum exosomes of PC patients and those from control patients. Then, bioinformatics methods were used to analyze the functions of the identified proteins, and the possible functions were verified through cell culture experiments.
RESULTS
A total of 611 proteins were identified from exosomes, and 141 proteins were differentially expressed, with 91 up- and 50 down regulated proteins in PC cancer compared to healthy controls. Further analysis indicated that APOE serves as an important hub in the network. In addition, CRP, VWF, APOA2, NIN, and GSK3B potentially interact with many other proteins. We then tested the effect of patient serum-derived exosomes on pancreatic cancer cells and found that patient serum-derived exosomes, but not those from healthy controls, induced cell proliferation, migration, and EMT, supporting the role of exosomes in metastasis.
CONCLUSION
Our data suggest that exosomes derived from PC patients may promote PC metastasis.
背景
胰腺癌（PC）是侵袭性最强的恶性肿瘤之一，尽管已进行了广泛研究，但其预后仍然很差。血清来源的外泌体在胰腺癌发生和发展中的作用仍不清楚。
方法
本研究采用基于iTRAQ的蛋白质组学分析来寻找胰腺癌患者与对照患者血清外泌体之间的差异。然后，使用生物信息学方法分析已鉴定蛋白质的功能，并通过细胞培养实验验证可能的功能。
结果
从外泌体中总共鉴定出611种蛋白质，其中141种蛋白质差异表达，与健康对照相比，胰腺癌中有91种上调和50种下调的蛋白质。进一步分析表明，载脂蛋白E（APOE）在该网络中起重要枢纽作用。此外，C反应蛋白（CRP）、血管性血友病因子（VWF）、载脂蛋白A2（APOA2）、神经生长抑制因子（NIN）和糖原合成酶激酶3β（GSK3B）可能与许多其他蛋白质相互作用。然后，我们测试了患者血清来源的外泌体对胰腺癌细胞的影响，发现患者血清来源的外泌体而非健康对照者的外泌体可诱导细胞增殖、迁移和上皮-间质转化（EMT），支持外泌体在转移中的作用。
结论
我们的数据表明，胰腺癌患者来源的外泌体可能促进胰腺癌转移。
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