Detection of phosphatidylserine-positive exosomes as a diagnostic marker for ovarian malignancies: a proof of concept study
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Jayanthi Lea1, Raghava Sharma2, Fan Yang2, Hong Zhu1, E. Sally Ward3,4 and Alan J. Schroit1,3
1 Harold Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA
2 Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA
3 Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA
4 Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX, USA
Alan J. Schroit, email:
Keywords: phosphatidylserine, extracellular vesicles, ovarian malignancies, exosomes
Received: January 04, 2017 Accepted: January 11, 2017 Published: January 22, 2017
There are no suitable screening modalities for ovarian carcinomas (OC) and repeated imaging and CA-125 levels are often needed to triage equivocal ovarian masses. Definitive diagnosis of malignancy, however, can only be established by histologic confirmation. Thus, the ability to detect OC at early stages is low, and most cases are diagnosed as advanced disease. Since tumor cells expose phosphatidylserine (PS) on their plasma membrane, we predicted that tumors might secrete PS-positive exosomes into the bloodstream that could be a surrogate biomarker for cancer. To address this, we developed a highly stringent ELISA that detects picogram quantities of PS in patient plasma. Blinded plasma from 34 suspect ovarian cancer patients and 10 healthy subjects were analyzed for the presence of PS-expressing vesicles. The nonparametric Wilcoxon rank sum test showed the malignant group had significantly higher PS values than the benign group (median 0.237 vs. -0.027, p=0.0001) and the malignant and benign groups had significantly higher PS values than the healthy group (median 0.237 vs -0.158, p<0.0001 and -0.027 vs -0.158, p=0.0002, respectively). ROC analysis of the predictive accuracy of PS-expressing exosomes/vesicles in predicting malignant against normal, benign against normal and malignant against benign revealed AUCs of 1.0, 0.95 and 0.911, respectively. This study provides proof-of-concept data that supports the high diagnostic power of PS detection in the blood of women with suspect ovarian malignancies.
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