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World Journal of Surgical Oncology
Published in: World Journal of Surgical Oncology 1/2014

Open Access 01-12-2014 | Research

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

Authors: Heejeong Lee, Kyu Rae Kim, Nam Hoon Cho, Sung Ran Hong, Hoiseon Jeong, Sun Young Kwon, Kwang Hwa Park, Hee Jung An, Tae Heon Kim, Insun Kim, Hye Kyoung Yoon, Kwang Sun Suh, Ki Ouk Min, Hyun Joo Choi, Ji Young Park, Chong Woo Yoo, Youn Soo Lee, Hee Jin Lee, Weon Sun Lee, Chul Soo Park, Yonghee Lee, The Gynecological Pathology Study Group of the Korean Society of Pathologists

Published in: World Journal of Surgical Oncology | Issue 1/2014

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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.
Appendix
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Metadata
Title
MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix
Authors
Heejeong Lee
Kyu Rae Kim
Nam Hoon Cho
Sung Ran Hong
Hoiseon Jeong
Sun Young Kwon
Kwang Hwa Park
Hee Jung An
Tae Heon Kim
Insun Kim
Hye Kyoung Yoon
Kwang Sun Suh
Ki Ouk Min
Hyun Joo Choi
Ji Young Park
Chong Woo Yoo
Youn Soo Lee
Hee Jin Lee
Weon Sun Lee
Chul Soo Park
Yonghee Lee
The Gynecological Pathology Study Group of the Korean Society of Pathologists
Publication date
01-12-2014
Publisher
BioMed Central
Published in
World Journal of Surgical Oncology / Issue 1/2014
Electronic ISSN: 1477-7819
DOI
https://doi.org/10.1186/1477-7819-12-334

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