Ovarian cancer circulating extracelluar vesicles promote coagulation and have a potential in diagnosis: an iTRAQ based proteomic analysis
Authors: Zhang, Wei; Peng, Peng; Ou, Xiaoxuan; Shen, Keng; Wu, Xiaohua
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 (5.350.14 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.
A novel splice-site mutation c.42-2A > T (IVS1-2A > T) of SERPINC1 in a Korean family with inherited antithrombin deficiency
BLOOD COAGULATION & FIBRINOLYSIS
Authors: Jang, Moon Ju; Lee, Jeong-Guil; Chong, So Young; Huh, Ji Young; Jang, Mi-Ae; Kim, Hee-Jin; Oh, Doyeun
Inherited antithrombin (AT) deficiency (OMIM 107300) is an autosomal dominant disorder and causes a 20-fold increase in the risk of venous thromboembolism. Herein, we describe a case of a novel splice-site mutation in the SERPINC1 gene in a Korean patient with inherited AT deficiency. The patient was a 35-year-old woman who presented with deep vein thrombosis (DVT) and pulmonary embolism and was without a recent history of any precipitating factors. The obtaining of her family history revealed that her mother had an ischemic stroke and a pulmonary embolism and her two sisters both had an episode of DVT during pregnancy. DNA sequencing of SERPINC1 revealed the novel variant IVS1-2A>T (c.42-2A>T), a substitution in intron 1, in the proband and her daughter. The mutation IVS1-2A>T eliminates the acceptor splice-site of intron 1. The present case is the first novel splice-site mutation of SERPINC1 in a Korean family with inherited AT deficiency. Blood Coagul Fibrinolysis 22:742-745 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.