title: Detection of phosphatidylserine-positive exosomes as a diagnostic marker for ovarian malignancies: a proof of concept study.
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.
authors.affiliation: Harold Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Jayanthi
authors.initials: J
authors.lastname: Lea
authors.affiliation: Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Raghava
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Harold Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA.|Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX, USA.
authors.forename: E Sally
authors.initials: ES
authors.lastname: Ward
authors.affiliation: Harold Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA.|Department of Immunology, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Schroit
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000097:blood / Q000175:diagnosis*; D002288:Adenocarcinoma, Mucinous / Q000097:blood / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D018284:Cystadenocarcinoma, Serous / Q000097:blood / Q000175:diagnosis*; D016889:Endometrial Neoplasms / Q000097:blood / Q000175:diagnosis*; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis*; D010718:Phosphatidylserines / Q000097:blood*; D011379:Prognosis; D012372:ROC Curve; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D010718:Phosphatidylserines
keywords: exosomes; extracellular vesicles; ovarian malignancies; phosphatidylserine