TY - JOUR
T1 - Detection of phosphatidylserine-positive exosomes as a diagnostic marker for ovarian malignancies
T2 - A proof of concept study
AU - Lea, Jayanthi
AU - Sharma, Raghava
AU - Yang, Fan
AU - Zhu, Hong
AU - Sally Ward, E.
AU - Schroit, Alan J.
PY - 2017
Y1 - 2017
N2 - 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 proofof- concept data that supports the high diagnostic power of PS detection in the blood of women with suspect ovarian malignancies.
AB - 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 proofof- concept data that supports the high diagnostic power of PS detection in the blood of women with suspect ovarian malignancies.
KW - Exosomes
KW - Extracellular vesicles
KW - Ovarian malignancies
KW - Phosphatidylserine
UR - http://www.scopus.com/inward/record.url?scp=85014091849&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014091849&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.14795
DO - 10.18632/oncotarget.14795
M3 - Article
C2 - 28122335
AN - SCOPUS:85014091849
SN - 1949-2553
VL - 8
SP - 14395
EP - 14407
JO - Oncotarget
JF - Oncotarget
IS - 9
ER -