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


CONCLUSIONS
Measurement of tissue and plasma EEC-associated miRNAs may be useful for early detection, diagnostic, and follow-up tests for EEC.
Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Ozora
O
Tsukamoto
Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. Electronic address: kiyonori@nagasaki-u.ac.jp.
Kiyonori
K
Miura
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Hiroyuki
H
Mishima
Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Shuhei
S
Abe
Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Masanori
M
Kaneuchi
Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Ai
A
Higashijima
Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Shoko
S
Miura
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Akira
A
Kinoshita
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Koh-ichiro
K
Yoshiura
Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Hideaki
H
Masuzaki
D000328:Adult; D018269:Carcinoma, Endometrioid / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D016889:Endometrial Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007044:Hysterectomy; D035683:MicroRNAs / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D020133:Reverse Transcriptase Polymerase Chain Reaction
D035683:MicroRNAs
Endometrioid endometrial carcinoma; MiRNA; Next-generation sequencing; Plasma; Tissue