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MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix

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Author(s)
Heejeong LeeKyu Rae KimNam Hoon ChoSung Ran HongHoiseon JeongSun Young KwonKwang Hwa ParkHee Jung AnTae Heon KimInsun KimHye Kyoung YoonKwang Sun SuhKi Ouk MinHyun Joo ChoiJi Young ParkChong Woo YooYoun Soo LeeHee Jin LeeWeon Sun LeeChul Soo ParkYonghee Lee
Keimyung Author(s)
Kwon, Sun Young
Department
Dept. of Pathology (병리학)
Journal Title
World Journal of Surgical Oncology
Issued Date
2014
Volume
12
Issue
1
Keyword
microRNAMinimal deviation adenocarcinomaNotchUterine cervix
Abstract
Background

MicroRNA (miRNA) expression is known to be deregulated in cervical carcinomas. However, no data is available about the miRNA expression pattern for the minimal deviation adenocarcinoma (MDA) of uterine cervix. We sought to detect deregulated miRNAs in MDA in an attempt to find the most dependable miRNA or their combinations to understand their tumorigenesis pathway and to identify diagnostic or prognostic biomarkers. We also investigated the association between those miRNAs and their target genes, especially Notch1 and Notch2.


Methods

We evaluated miRNA expression profiles via miRNA microarray and validated them using.real-time PCR assays with 24 formalin-fixed, paraffin-embedded tissue blocks of MDA and 11 normal proliferative endocervical tissues as control. Expression for Notch1 and 2 was assessed by immunohistochemistry.


Results

MiRNA-135a-3p, 192-5p, 194-5p, and 494 were up-regulated, whereas miR-34b-5p, 204-5p, 299-5p, 424-5p, and 136-3p were down-regulated in MDA compared with normal proliferative endocervical tissues (all P <0.05). Considering the second-order Akaike Information Criterion consisting of likelihood ratio and number of parameters, miR-34b-5p showed the best discrimination power among the nine candidate miRNAs. A combined panel of miR-34b-5p and 194-5p was the best fit model to discriminate between MDA and control, revealing 100% sensitivity and specificity. Notch1 and Notch2, respective target genes of miR-34b-5p and miR-204-5p, were more frequently expressed in MDA than in control (63% vs. 18%; 52% vs. 18%, respectively, P <0.05). MiR-34b-5p expression level was higher in Notch1-negative samples compared with Notch1-positive ones (P <0.05). Down-regulated miR-494 was associated with poor patient survival (P =0.036).


Conclusions

MDA showed distinctive expression profiles of miRNAs, Notch1, and Notch2 from normal proliferative endocervical tissues. In particular, miR-34b-5p and 194-5p might be used as diagnostic biomarkers and miR-494 as a prognostic predictor for MDA. The miR-34b-5p/Notch1 pathway as well as Notch2 might be important oncogenic contributors to MDA.


Electronic supplementary material

The online version of this article (doi:10.1186/1477-7819-12-334) contains supplementary material, which is available to authorized users.

Keywords: microRNA, Minimal deviation adenocarcinoma, Notch, Uterine cervix
Keimyung Author(s)(Kor)
권선영
Publisher
School of Medicine
Citation
Heejeong Lee et al. (2014). MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix. World Journal of Surgical Oncology, 12(1), 334–334. doi: 10.1186/1477-7819-12-334
Type
Article
ISSN
1477-7819
DOI
10.1186/1477-7819-12-334
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/34807
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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