Abstract
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.
Highlights
The detection of tumor-specific signatures in patient plasma has recently come to the forefront of cancer diagnosis
Because exosome membranes are derived from plasma membrane of the parent cell, these findings raise the possibility that unlike exosomes released from normal cells, exosomes derived from tumor cells, might expose PS
In a blind retrospective study carried out in accordance with guidelines for reporting of tumor marker studies (REMARK) [15] and standards for reporting diagnostic test accuracy (STARD) [16], we show that the presence of PS in blood accurately detects ovarian cancers and differentiates between patients with benign and malignant disease
Summary
The detection of tumor-specific signatures in patient plasma has recently come to the forefront of cancer diagnosis. Specific tumor markers can be indicative of cancer type, a surrogate pan cancer-specific marker could be useful in the general diagnosis of cancer, differentiate between benign and malignant status of uncertain radiographic/ sonographic lesions and serve as a predictive marker for recurrence and response to therapy. This is relevant for ovarian cancers where there is currently no routine screening test. Exosomes are 100-200 nm vesicles that are secreted to the extracellular space and peripheral circulation by most cells They are formed by the inward budding of plasma membrane-derived multivesicular bodies that entrap nucleic acid and protein-rich cytosol. PSexpressing exosomes are secreted from in vitro cultivated ovarian carcinoma (OC) cell lines and are found in ascites from OC patients [11,12,13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
