World journal of surgical oncology · 2014
MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix.
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Lee Heejeong, Kim Kyu Rae, Cho Nam Hoon, Hong Sung Ran, Jeong Hoiseon, Kwon Sun Young, Park Kwang Hwa, An Hee Jung, Kim Tae Heon, Kim Insun, Yoon Hye Kyoung, Suh Kwang Sun, Min Ki Ouk, Choi Hyun Joo, Park Ji Young, Yoo Chong Woo, Lee Youn Soo, Lee Hee Jin, Lee Weon Sun, Park Chul Soo, Lee Yonghee, Gynecological Pathology Study Group of the Korean Society of Pathologists
Аннотация
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.
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.
Предметные рубрики MeSH
AdenocarcinomaAdultBiomarkers, TumorCase-Control StudiesCervix UteriFemaleFollow-Up StudiesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMicroRNAsMiddle AgedNeoplasm MetastasisNeoplasm StagingPrognosisROC CurveReal-Time Polymerase Chain ReactionReceptor, Notch1Receptor, Notch2Survival RateUterine Cervical Neoplasms