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Plasma miRNAs as diagnostic and prognostic biomarkers for ovarian cancer.

Zheng H, Zhang L, Zhao Y, Yang D, Song F, Wen Y, Hao Q, Hu Z, Zhang W, Chen K - PLoS ONE (2013)

Bottom Line: We found higher plasma miR-205 and lower let-7f expression in cases than in controls.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT

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.

Methodology/principal findings: 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/significance: 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.

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Related in: MedlinePlus

ROC of the panel (miR-205 and let-7f) for EOC cases.We established the miR-205 and let-7f panel in validation phase I and confirmed it in independent samples in phase II. In phase I, (A) the AUC was 0.831 (95% CI, 0.772 to 0.880; sensitivity = 62.4%, specificity = 92.9%) for cases; (B) 0.895 (95% CI, 0.822 to 0.967; sensitivity = 77.8%, specificity = 90.0%) for early-stage cases versus controls; and (C) 0.814 (95% CI, 0.700 to 0.929; sensitivity = 68.4%, specificity = 92.9%) for low CA-125 (<35 U/ml) cases versus controls. In phase II, (D) the AUC was 0.813 (95% CI, 0.759 to 0.860; sensitivity = 71.3%, specificity = 82.0%) for cases versus controls; (E) 0.783 (95% CI, 0.699 to 0.853; sensitivity = 70.0%, specificity = 82.0%) for early-stage cases versus controls; and (F) 0.726 (95% CI, 0.634 to 0.805; sensitivity = 64.3%, specificity = 72.0%) for low CA-125 (<35 U/ml) cases versus controls.
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pone-0077853-g003: ROC of the panel (miR-205 and let-7f) for EOC cases.We established the miR-205 and let-7f panel in validation phase I and confirmed it in independent samples in phase II. In phase I, (A) the AUC was 0.831 (95% CI, 0.772 to 0.880; sensitivity = 62.4%, specificity = 92.9%) for cases; (B) 0.895 (95% CI, 0.822 to 0.967; sensitivity = 77.8%, specificity = 90.0%) for early-stage cases versus controls; and (C) 0.814 (95% CI, 0.700 to 0.929; sensitivity = 68.4%, specificity = 92.9%) for low CA-125 (<35 U/ml) cases versus controls. In phase II, (D) the AUC was 0.813 (95% CI, 0.759 to 0.860; sensitivity = 71.3%, specificity = 82.0%) for cases versus controls; (E) 0.783 (95% CI, 0.699 to 0.853; sensitivity = 70.0%, specificity = 82.0%) for early-stage cases versus controls; and (F) 0.726 (95% CI, 0.634 to 0.805; sensitivity = 64.3%, specificity = 72.0%) for low CA-125 (<35 U/ml) cases versus controls.

Mentions: A stepwise logistic regression model was used to estimate the joint power of miR-205 and let-7f at predicting the risk of EOC in the validation phase I set. MiR-205 and let-7f were effective at discriminating cases from controls [Fig. S1A; logit (P = EOC) = −0.610−3.075×let-7f+1.532×miR-205 was used to construct the ROC curve]. The AUC of the miRNA panel (let-7f and miR-205) was 0.831 (95% CI, 0.772 to 0.880; sensitivity = 62.4%, specificity = 92.9%) (Fig. 3A), which was significantly higher than the AUCs of miR-205 (P<0.001) and let-7f (P = 0.008) alone (Fig. S1B).


Plasma miRNAs as diagnostic and prognostic biomarkers for ovarian cancer.

Zheng H, Zhang L, Zhao Y, Yang D, Song F, Wen Y, Hao Q, Hu Z, Zhang W, Chen K - PLoS ONE (2013)

ROC of the panel (miR-205 and let-7f) for EOC cases.We established the miR-205 and let-7f panel in validation phase I and confirmed it in independent samples in phase II. In phase I, (A) the AUC was 0.831 (95% CI, 0.772 to 0.880; sensitivity = 62.4%, specificity = 92.9%) for cases; (B) 0.895 (95% CI, 0.822 to 0.967; sensitivity = 77.8%, specificity = 90.0%) for early-stage cases versus controls; and (C) 0.814 (95% CI, 0.700 to 0.929; sensitivity = 68.4%, specificity = 92.9%) for low CA-125 (<35 U/ml) cases versus controls. In phase II, (D) the AUC was 0.813 (95% CI, 0.759 to 0.860; sensitivity = 71.3%, specificity = 82.0%) for cases versus controls; (E) 0.783 (95% CI, 0.699 to 0.853; sensitivity = 70.0%, specificity = 82.0%) for early-stage cases versus controls; and (F) 0.726 (95% CI, 0.634 to 0.805; sensitivity = 64.3%, specificity = 72.0%) for low CA-125 (<35 U/ml) cases versus controls.
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pone-0077853-g003: ROC of the panel (miR-205 and let-7f) for EOC cases.We established the miR-205 and let-7f panel in validation phase I and confirmed it in independent samples in phase II. In phase I, (A) the AUC was 0.831 (95% CI, 0.772 to 0.880; sensitivity = 62.4%, specificity = 92.9%) for cases; (B) 0.895 (95% CI, 0.822 to 0.967; sensitivity = 77.8%, specificity = 90.0%) for early-stage cases versus controls; and (C) 0.814 (95% CI, 0.700 to 0.929; sensitivity = 68.4%, specificity = 92.9%) for low CA-125 (<35 U/ml) cases versus controls. In phase II, (D) the AUC was 0.813 (95% CI, 0.759 to 0.860; sensitivity = 71.3%, specificity = 82.0%) for cases versus controls; (E) 0.783 (95% CI, 0.699 to 0.853; sensitivity = 70.0%, specificity = 82.0%) for early-stage cases versus controls; and (F) 0.726 (95% CI, 0.634 to 0.805; sensitivity = 64.3%, specificity = 72.0%) for low CA-125 (<35 U/ml) cases versus controls.
Mentions: A stepwise logistic regression model was used to estimate the joint power of miR-205 and let-7f at predicting the risk of EOC in the validation phase I set. MiR-205 and let-7f were effective at discriminating cases from controls [Fig. S1A; logit (P = EOC) = −0.610−3.075×let-7f+1.532×miR-205 was used to construct the ROC curve]. The AUC of the miRNA panel (let-7f and miR-205) was 0.831 (95% CI, 0.772 to 0.880; sensitivity = 62.4%, specificity = 92.9%) (Fig. 3A), which was significantly higher than the AUCs of miR-205 (P<0.001) and let-7f (P = 0.008) alone (Fig. S1B).

Bottom Line: We found higher plasma miR-205 and lower let-7f expression in cases than in controls.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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT

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.

Methodology/principal findings: 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/significance: 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.

Show MeSH
Related in: MedlinePlus