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人乳头瘤病毒阳性与阴性口咽癌中微小RNA的比较分析。

Comparative analysis of micro-RNAs in human papillomavirus-positive versus -negative oropharyngeal cancers.

作者信息

Mirghani Haitham, Ugolin Nicolas, Ory Catherine, Goislard Maud, Lefèvre Marine, Baulande Sylvain, Hofman Paul, Guily Jean Lacau St, Chevillard Sylvie, Lacave Roger

机构信息

ER2 Unit and GRC10, Université Pierre et Marie Curie, Paris, France.

Department of Head and Neck Surgery, Institut de Cancérologie Gustave Roussy, Villejuif, France.

出版信息

Head Neck. 2016 Nov;38(11):1634-1642. doi: 10.1002/hed.24487. Epub 2016 Apr 21.

Abstract

BACKGROUND

Oncogenic mechanisms of human papillomavirus (HPV)-positive oropharyngeal cancer are still poorly characterized. Analysis of their microRNA expression profile might provide valuable information.

METHODS

The microRNA expression profiles were analyzed by micro-arrays in 26 oropharyngeal cancers. A microRNA signature specific to HPV-status was identified by analyzing a learning/training set consisting of 16 oropharyngeal cancers. The robustness of this signature was further confirmed by blind case-by-case classification of a validation set composed of 10 independent tumors. Putative targeted molecular pathways were proposed using DIANA miRPath online software (http://microrna.gr/mirpath).

RESULTS

We have identified 25 miRNA signatures, which discriminates HPV16-positive oropharyngeal cancer from their HPV-negative counterparts. These 25 microRNAs play a potential role in Wnt and PI3K-pathways, cell-adhesion/cell-polarity, and the cytoskeleton regulation.

CONCLUSION

Our study contributes to a better understanding of pathogenic mechanisms involved in the development of HPV-positive oropharyngeal cancer and in the identification of potential therapeutic molecular targets. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016.

摘要

背景

人乳头瘤病毒(HPV)阳性口咽癌的致癌机制仍未得到充分描述。对其微小RNA表达谱的分析可能会提供有价值的信息。

方法

通过微阵列分析了26例口咽癌的微小RNA表达谱。通过分析由16例口咽癌组成的学习/训练集,确定了特定于HPV状态的微小RNA特征。通过对由10个独立肿瘤组成的验证集进行逐例盲法分类,进一步证实了该特征的稳健性。使用DIANA miRPath在线软件(http://microrna.gr/mirpath)提出了推定的靶向分子途径。

结果

我们鉴定出25种微小RNA特征,可将HPV16阳性口咽癌与其HPV阴性对应物区分开来。这25种微小RNA在Wnt和PI3K途径、细胞粘附/细胞极性以及细胞骨架调节中发挥潜在作用。

结论

我们的研究有助于更好地理解HPV阳性口咽癌发生发展过程中的致病机制,并有助于识别潜在的治疗分子靶点。©2016威利期刊公司。《头颈》38:1708 - 1716,2016年。

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