Haitham Mirghani1,2, Nicolas Ugolin3, Catherine Ory3, Maud Goislard3, Marine Lefèvre4, Sylvain Baulande5, Paul Hofman6, Jean Lacau St Guily7,8, Sylvie Chevillard3, Roger Lacave7,9. 1. ER2 Unit and GRC10, Université Pierre et Marie Curie, Paris, France. haitham.mirghani@gustaveroussy.fr. 2. Department of Head and Neck Surgery, Institut de Cancérologie Gustave Roussy, Villejuif, France. haitham.mirghani@gustaveroussy.fr. 3. CEA, DSV, iRCM, Laboratory of Experimental Cancerology, Fontenay-aux-Roses, Cedex, France. 4. Department of Pathology, GHUEP, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France. 5. PartnerChip, Evry, France. 6. Laboratory of Clinical and Experimental Pathology and Biobank of CHUN, Pasteur Hospital, Nice, France. 7. ER2 Unit and GRC10, Université Pierre et Marie Curie, Paris, France. 8. Department of Otolaryngology - Head and Neck Surgery, GHUEP, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, France. 9. Tumours Genomic Unit, GHUEP, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, France.
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.
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.
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