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

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.

Keywords: PI3K pathway; Wnt pathway; gene expression profile; human papillomavirus 16; micro/miRNA; microarray; oropharyngeal/oropharynx cancer.