MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix.
MicroRNA expression profiling and Notch1 and Notch2 expression in minimal deviation adenocarcinoma of uterine cervix.
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DOI：
10.1186/1477-7819-12-334
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发表时间：
2014-11-08
影响因子：
3.2
通讯作者：
Gynecological Pathology Study Group of the Korean Society of Pathologists
中科院分区：
文献类型：
--
作者：
Lee H;Kim KR;Cho NH;Hong SR;Jeong H;Kwon SY;Park KH;An HJ;Kim TH;Kim I;Yoon HK;Suh KS;Min KO;Choi HJ;Park JY;Yoo CW;Lee YS;Lee HJ;Lee WS;Park CS;Lee Y;Gynecological Pathology Study Group of the Korean Society of Pathologists
已知微小RNA（miRNA）表达在宫颈癌中失调。然而，没有关于子宫颈微偏腺癌（MDA）的miRNA表达模式的数据。我们试图检测MDA中失调的miRNA，试图找到最可靠的miRNA或其组合，以了解其肿瘤发生途径并鉴定诊断或预后生物标志物。我们还研究了这些miRNAs与其靶基因，特别是Notch 1和Notch 2之间的关联。我们通过miRNA微阵列评估了miRNA表达谱，并使用实时PCR检测法对24例福尔马林固定、石蜡包埋的MDA组织块和11例正常增生的宫颈内膜组织进行了验证。Notch 1和2的表达通过免疫组织化学评估。与正常增生的宫颈内膜组织相比，MDA中miRNA-135 a-3 p、192- 5 p、194- 5 p和494表达上调，而miR-34 b-5 p、204- 5 p、299- 5 p、424- 5 p和136- 3 p表达下调（均P <0.05）。考虑到由似然比和参数数量组成的二阶Akaike信息准则，miR-34 b-5 p在9种候选miRNAs中显示出最好的区分能力。miR-34 b-5 p和194- 5 p的组合组是区分MDA和对照的最佳拟合模型，揭示了100%的灵敏度和特异性。miR-34 b-5 p和miR-204- 5 p的靶基因Notch 1和Notch 2在MDA中的表达率分别为63%和52%（P <0.05）。Notch 1阴性组miR-34 b-5 p表达水平高于Notch 1阳性组（P <0.05）。下调的miR-494与较差的患者存活率相关（P =0.036）。MDA在正常增生的宫颈内膜组织中显示出独特的miRNA、Notch 1和Notch 2表达谱。特别是，miR-34 b-5 p和194- 5 p可用作MDA的诊断生物标志物，而miR-494可用作MDA的预后预测因子。miR-34 b-5 p/Notch 1通路以及Notch 2可能是MDA的重要致癌贡献者。本文的在线版本（doi：10.1186/1477-7819-12-334）包含补充材料，可供授权用户使用。
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. 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. 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). 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. The online version of this article (doi:10.1186/1477-7819-12-334) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Deftereos G;Corrie SR;Feng Q;Morihara J;Stern J;Hawes SE;Kiviat NB
通讯作者：
Kiviat NB
影响因子：
4.7
作者：
Resnick, Kimberly E.;Alder, Hansjuerg;Cohn, David E.
通讯作者：
Cohn, David E.
影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
3.5
作者：
Ishii, K;Hosaka, N;Katsuyama, T
通讯作者：
Katsuyama, T
DOI：
10.1097/00004347-198302000-00005
发表时间：
1983-01-01
影响因子：
2.4
作者：
KAMINSKI, PF;NORRIS, HJ
通讯作者：
NORRIS, HJ