Plasma miRNAs as diagnostic and prognostic biomarkers for ovarian cancer.

Plasma miRNAs as diagnostic and prognostic biomarkers for ovarian cancer.
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血浆 miRNA 作为卵巢癌的诊断和预后生物标志物

DOI:
10.1371/journal.pone.0077853
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Chen K
Chen K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Zheng H;Zhang L;Zhao Y;Yang D;Song F;Wen Y;Hao Q;Hu Z;Zhang W;Chen K

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背景大多数(70%)上皮性卵巢癌(EOCs)诊断较晚。需要促进疾病检测和预测结果的非侵入性生物标志物。microRNA(miRNAs)是一类新的生物标志物。本研究旨在鉴定和验证血浆miRNAs作为EOC的生物标志物。方法/主要发现我们评估了来自两个机构的360名EOC患者和200名健康对照的血浆样本。将所有样本分组为筛选、训练和验证集。我们在筛选集中通过TaqMan低密度阵列扫描循环血浆miRNA,并在训练集中通过实时聚合酶链反应测定鉴定/验证miRNA标记。受试者操作特征和逻辑回归分析建立了诊断性miRNA组,并在验证集中得到证实。我们发现病例组血浆miR-205表达高于对照组,let-7 f表达低于对照组。miR-205和let-7 f一起提供了EOC的高诊断准确性,特别是在I期疾病患者中。这两种miRNAs与糖类抗原-125(CA-125)的组合进一步提高了检测的准确性。MiR-483- 5 p在III期和IV期的表达高于I期和II期,这与其在肿瘤组织中的表达模式一致。此外,let-7 f水平较低预示EOC患者预后不良。我们的研究结果表明,血浆miR-205和let-7 f是卵巢癌检测的生物标志物,补充CA-125; let-7 f可能预测卵巢癌预后。
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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