Ovarian cancer circulating extracelluar vesicles promote coagulation and have a potential in diagnosis: an iTRAQ based proteomic analysis

BMC Cancer

Wei Zhang¹  Xiaohua Wu¹  Xiaoxuan Ou¹  Keng Shen²  Peng Peng² 

[1] Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center;Department of Obstetrics and Gynecology Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College;

关键词: Epithelial ovarian cancer;    Extracellular vesicles;    Proteomics;    Biomarker;    Diagnosis;   

DOI  :  10.1186/s12885-019-6176-1

来源: DOAJ

【 摘 要 】

Abstract Background Circulating extracelluar vesicles (EVs) in epithelial ovarian cancer (EOC) patients emanate from multiple cells. These EVs are emerging as a new type of biomarker as they can be obtained by non-invasive approaches. The aim of this study was to investigate circulating EVs from EOC patients and healthy women to evaluate their biological function and potential as diagnostic biomarkers. Methods A quantitative proteomic analysis (iTRAQ) was applied and performed on 10 EOC patients with advanced stage (stage III–IV) and 10 controls. Twenty EOC patients and 20 controls were applied for validation. The candidate proteins were further validated in another 40-paired cohort to investigate their biomarker potential. Coagulation cascades activation was accessed by determining Factor X activity. Results Compared with controls, 200 proteins were upregulated and 208 proteins were downregulated in the EOC group. The most significantly involved pathway is complement and coagulation cascades. ApoE multiplexed with EpCAM, plg, serpinC1 and C1q provide optimal diagnostic information for EOC with AUC = 0.913 (95% confidence interval (CI) =0.848–0.957, p < 0.0001). Level of activated Factor X was significantly higher in EOC group than control (5.35 ± 0.14 vs. 3.69 ± 0.29, p < 0.0001). Conclusions Our study supports the concept of circulating EVs as a tool for non-invasive diagnosis of ovarian cancer. EVs also play pivotal roles in coagulation process, implying the inherent mechanism of generation of thrombus which often occurred in ovarian cancer patients at late stages.

【 授权许可】

Unknown