Proteomic Profiling of Serum Exosomes From Patients With Metastatic Gastric Cancer

被引:60
作者
Ding, Xiao-Qing [1 ]
Wang, Zhe-Ying [1 ]
Xia, Di [1 ]
Wang, Rui-Xian [1 ]
Pan, Xiao-Rong [1 ]
Tong, Jian-Hua [1 ]
机构
[1] Shanghai Jiao Tong Univ, Ruijin Hosp, Fac Med Lab Sci & Cent Lab, Sch Med, Shanghai, Peoples R China
来源
FRONTIERS IN ONCOLOGY | 2020年 / 10卷
基金
中国国家自然科学基金;
关键词
metastatic gastric cancer; exosomes; proteomics; proteasome; PSMA3; PSMA6; EXTRACELLULAR VESICLES; PANCREATIC-CANCER; COMMUNICATION; MICROVESICLES; ASSOCIATION; BIOGENESIS; SECRETION; BIOMARKER; FLUIDS;
D O I
10.3389/fonc.2020.01113
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background:Clinical management of metastatic gastric cancer (mGC) remains a major challenge due to a lack of specific biomarkers and effective therapeutic targets. Recently, accumulating evidence has suggested that exosomes play an essential role in cancer metastasis and can be an excellent reservoir of novel biomarkers and candidate therapeutic targets for cancer. Therefore, in this study, we aimed to reveal the proteomic profile of mGC-derived exosomes. Methods:Exosomes were isolated from pooled serum samples of 20 mGC patients and 40 healthy controls (HC) by ultracentrifugation. Next, quantitative proteomic analyses were applied to analyze the protein profiles of the exosomes, and bioinformatic analyses were conducted on the proteomic data. Finally, the expression of exosomal protein candidates was selectively validated in individual subjects by western blot analysis. Results:We isolated exosomes from serum samples. The size of the serum derived exosomes ranged from 30 to 150 nm in diameter. The exosomal markers CD9 and CD81 were observed in the serum exosomes. However, the exosomal negative marker calnexin, an endoplasmic reticulum protein, was not detected in exosomes. Overall, 443 exosomal proteins, including 110 differentially expressed proteins (DEPs) were identified by quantitative proteomics analyses. The bioinformatics analyses indicated that the upregulated proteins were enriched in the process of protein metabolic, whereas the downregulated proteins were largely involved in cell-cell adhesion organization. Surprisingly, 10 highly vital proteins (UBA52, PSMA1, PSMA5, PSMB6, PSMA7, PSMA4, PSMA3, PSMB1, PSMA6, and FGA) were filtered from DEPs, most of which are proteasome subunits. Moreover, the validation data confirmed that PSMA3 and PSMA6 were explicitly enriched in the serum derived exosomes from patients with mGC. Conclusion:The present study provided a comprehensive description of the serum exosome proteome of mGC patients, which could be an excellent resource for further studies of mGC.
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页数:13
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