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

The Gynecological Pathology Study Group of the Korean Society of Pathologists

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Article number334
JournalWorld Journal of Surgical Oncology
Volume12
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

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MicroRNAs
Cervix Uteri
Adenocarcinoma
Biomarkers
Paraffin
Formaldehyde
Genes
Real-Time Polymerase Chain Reaction
Carcinogenesis
Immunohistochemistry
Carcinoma
Sensitivity and Specificity
Survival

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

The Gynecological Pathology Study Group of the Korean Society of Pathologists. / MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix. In: World Journal of Surgical Oncology. 2014 ; Vol. 12, No. 1.
@article{52207d5d6feb4c06b81b5d491c7da5d0,
title = "MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine 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.",
author = "{The Gynecological Pathology Study Group of the Korean Society of Pathologists} and Heejeong Lee and Kim, {Kyu Rae} and Namhoon Cho and Hong, {Sung Ran} and Hoiseon Jeong and Kwon, {Sun Young} and Park, {Kwang Hwa} and An, {Hee Jung} and Kim, {Tae Heon} and Insun Kim and Yoon, {Hye Kyoung} and Suh, {Kwang Sun} and Min, {Ki Ouk} and Choi, {Hyun Joo} and Park, {Ji Young} and Yoo, {Chong Woo} and Lee, {Youn Soo} and Lee, {Hee Jin} and Lee, {Weon Sun} and Park, {Chul Soo} and Yonghee Lee",
year = "2014",
month = "1",
day = "1",
doi = "10.1186/1477-7819-12-334",
language = "English",
volume = "12",
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MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix. / The Gynecological Pathology Study Group of the Korean Society of Pathologists.

In: World Journal of Surgical Oncology, Vol. 12, No. 1, 334, 01.01.2014.

Research output: Contribution to journalArticle

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, Namhoon

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

PY - 2014/1/1

Y1 - 2014/1/1

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

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VL - 12

JO - World Journal of Surgical Oncology

JF - World Journal of Surgical Oncology

SN - 1477-7819

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ER -