Identification of endometrioid endometrial carcinoma-associated microRNAs in tissue and plasma

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• 作者：Ozora Tsukamoto^a ; Kiyonori Miura^a ; ^{kiyonori@nagasaki-u.ac.jp" class="auth_mail} ; Hiroyuki Mishima^b ; Shuhei Abe^a ; Masanori Kaneuchi^a ; Ai Higashijima^a ; Shoko Miura^a ; Akira Kinoshita^b ; Koh-ichiro Yoshiura^b ; Hideaki Masuzaki^a
• 关键词：Endometrioid endometrial carcinoma ; Next-generation sequencing ; MiRNA ; Tissue ; Plasma
• 刊名：Gynecologic Oncology
• 出版年：March, 2014
• 年：2014
• 卷：132
• 期：3
• 页码：715-721
• 全文大小：359 K

文摘

Objective

This study aimed to identify a set of endometrioid endometrial carcinoma EEC-associated microRNAs (miRNAs) in tissue and plasma, and evaluate their clinical significance.

Methods

A set of EEC-associated miRNAs in tissue and plasma was identified by next-generation sequencing (NGS), which could enable in-depth characterization of the global repertoire of miRNAs.

Results

NGS identified 11 candidate EEC-associated miRNAs. Quantitative reverse-transcriptase PCR identified 8 EEC-associated miRNAs in tissue (upregulated: miR-499, miR-135b, miR-205, downregulated: miR-10b, miR-195, miR-30a-5p, miR-30a-3p and miR-21). Expression of hsa-miR-499 in International Federation of Gynecology and Obstetrics (FIGO) Stage IA and Grade 1 tissues was significantly lower than in others (FIGO Stage IB or more advanced, and Grade 2 or 3). By receiver operating characteristic (ROC) curve analysis, compared with single EEC-associated miRNA, two miRNA signatures (miR135b/miR195 and miR135b/miR30a-3p) could distinguish between EEC and normal endometrial tissue samples yielding a high area under the curve (AUC) of 0.9835 [95% confidence interval (CI): 0.9677-1.0], and 0.9898 (95% CI: 0.9677-1.0), respectively. As possible non-invasive markers for EEC, four EEC-associated miRNAs (increased level: miR-135b and miR-205, decreased-level: miR-30a-3p and miR-21) in plasma were identified. Circulating levels of three EEC-associated miRNAs (miR-135b, miR-205 and miR-30a-3p) in plasma were significantly decreased after hysterectomy. ROC curves analysis revealed that miR-135b and miR-205 levels in plasma yielded AUCs of 0.9722 (95% CI: 0.913-1.0) and 1.0 (95% CI: 1.0-1.0), respectively.

Conclusion

Measurement of tissue and plasma EEC-associated miRNAs may be useful for early detection, diagnostic, and follow-up tests for EEC.