TY - JOUR
T1 - MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix
AU - The Gynecological Pathology Study Group of the Korean Society of Pathologists
AU - Lee, Heejeong
AU - Kim, Kyu Rae
AU - Cho, Nam Hoon
AU - Hong, Sung Ran
AU - Jeong, Hoiseon
AU - Kwon, Sun Young
AU - Park, Kwang Hwa
AU - An, Hee Jung
AU - Kim, Tae Heon
AU - Kim, Insun
AU - Yoon, Hye Kyoung
AU - Suh, Kwang Sun
AU - Min, Ki Ouk
AU - Choi, Hyun Joo
AU - Park, Ji Young
AU - Yoo, Chong Woo
AU - Lee, Youn Soo
AU - Lee, Hee Jin
AU - Lee, Weon Sun
AU - Park, Chul Soo
AU - Lee, Yonghee
N1 - Funding Information:
This study was supported by a grant from the Institute of Clinical Medicine Research of Bucheon St. Mary’s Hospital, The Catholic University of Korea.
Publisher Copyright:
© 2014 Lee et al.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1186/1477-7819-12-334
DO - 10.1186/1477-7819-12-334
M3 - Article
C2 - 25381598
AN - SCOPUS:84922726697
SN - 1477-7819
VL - 12
JO - World Journal of Surgical Oncology
JF - World Journal of Surgical Oncology
IS - 1
M1 - 334
ER -