Plasma miRNAs as diagnostic and prognostic biomarkers for ovarian cancer.
BACKGROUND
Most (70%) epithelial ovarian cancers (EOCs) are diagnosed late. Non-invasive biomarkers that facilitate disease detection and predict outcome are needed. The microRNAs (miRNAs) represent a new class of biomarkers. This study was to identify and validate plasma miRNAs as biomarkers in EOC.


RESULTS
We evaluated plasma samples of 360 EOC patients and 200 healthy controls from two institutions. All samples were grouped into screening, training and validation sets. We scanned the circulating plasma miRNAs by TaqMan low-density array in the screening set and identified/validated miRNA markers by real-time polymerase chain reaction assay in the training set. Receiver operating characteristic and logistic regression analyses established the diagnostic miRNA panel, which were confirmed in the validation sets. We found higher plasma miR-205 and lower let-7f expression in cases than in controls. MiR-205 and let-7f together provided high diagnostic accuracy for EOC, especially in patients with stage I disease. The combination of these two miRNAs and carbohydrate antigen-125 (CA-125) further improved the accuracy of detection. MiR-483-5p expression was elevated in stages III and IV compared with in stages I and II, which was consistent with its expression pattern in tumor tissues. Furthermore, lower levels of let-7f were predictive of poor prognosis in EOC patients.


CONCLUSIONS
Our findings indicate that plasma miR-205 and let-7f are biomarkers for ovarian cancer detection that complement CA-125; let-7f may be predictive of ovarian cancer prognosis.
Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, P.R. China ; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, P.R. China.
Hong
H
Zheng
Lina
L
Zhang
Yanrui
Y
Zhao
Da
D
Yang
Fengju
F
Song
Yang
Y
Wen
Quan
Q
Hao
Zhibin
Z
Hu
Wei
W
Zhang
Kexin
K
Chen
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies
D014408:Biomarkers, Tumor; D035683:MicroRNAs; C534425:MIR205, human; C487931:mirnlet7 microRNA, human