miRNA-200a/c as potential biomarker in epithelial ovarian cancer (EOC): evidence based on miRNA meta-signature and clinical investigations.
miRNA-200a/c as potential biomarker in epithelial ovarian cancer (EOC): evidence based on miRNA meta-signature and clinical investigations.
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miRNA-200a/c 作为上皮性卵巢癌 (EOC) 的潜在生物标志物：基于 miRNA 元特征和临床研究的证据
DOI：
10.18632/oncotarget.13154
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发表时间：
2016-12-06
期刊：
影响因子：
--
通讯作者：
Qu K
中科院分区：
文献类型：
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作者：
Teng Y;Su X;Zhang X;Zhang Y;Li C;Niu W;Liu C;Qu K
上皮性卵巢癌（EOC）中的miRNA表达特征已被广泛研究。不幸的是，一致的结论很少从不同的研究，主要是由于高实验室间的变异性和小样本量。为了克服上述局限性，采用稳健秩聚合（Robust Rank Aggregation，RRA）方法对miRNA表达特征进行综合分析。采用诊断分析、Kaplan-Meier生存曲线和途径富集分析等方法，探讨meta signature miRNAs的临床应用价值和生物学功能。共纳入519例EOC和248例非癌样本。通过RRA方法鉴定了7个主要失调的miRNAs，其中2个miRNAs（miR-200 a-3 p和miR-200 c-3 p）经Bonferroni校正后仍有统计学意义。诊断荟萃分析显示miR-200 a-3 p（合并灵敏度为0.84，特异性为0.83）和miR-200 c-3 p（合并灵敏度为0.75，特异性为0.66）对EOC具有可靠的诊断能力。途径富集分析和表达相关性分析提示miR-200 a/c可能通过影响细胞黏附过程参与EOC的进展。基于两个独立队列的Kaplan-Meier生存分析显示，miR-200 a/c与EOC患者的总生存期之间存在强相关性。miR-200 a/c是EOC中表达最异常的miRNAs，可能成为EOC诊断和预后的新生物标志物。
Extensive effort has been put on miRNA expression signatures in epithelial ovarian cancer (EOC). Unfortunately, consistent conclusion rarely yielded from diverse studies, mainly due to the high inter-lab variability and small sample sizes. To overcome above limitations, an integrated analysis of miRNA expression signature was performed by employing Robust Rank Aggregation (RRA) method. Diagnostic analysis, Kaplan-Meier survival curves and pathway enrichment analysis were used to investigate the clinical values and biological functions of meta-signature miRNAs. A total of 519 EOC and 248 noncancerous samples were included. Seven mostly dysregulated miRNAs were identified by RRA method and two miRNAs (miR-200a-3p and miR-200c-3p) remained statistically significant after Bonferroni-correction. Diagnostic meta-analysis showed reliable diagnostic capacity of miR-200a-3p (with a pooled sensitivity of 0.84 and specificity of 0.83) and miR-200c-3p (with a pooled sensitivity of 0.75 and specificity of 0.66) for EOC. Pathway enrichment analysis and expression correlation analysis suggested miR-200a/c might contribute EOC progression by affecting cellular adhesion process. Kaplan-Meier survival analysis based on two independent cohorts revealed a strong association between miR-200a/c and overall survival in EOC patients. miR-200a/c was identified as the mostly dysregulated miRNAs in EOC and might be novel diagnostic and prognostic biomarkers for patients with EOC.