title: Comparison of the miRNA profiles in HPV-positive and HPV-negative tonsillar tumors and a model system of human keratinocyte clones.
abstract: Better insights into the molecular changes involved in virus-associated and -independent head and neck cancer may advance our knowledge of HNC carcinogenesis and identify critical disease biomarkers. Here we aimed to characterize the expression profiles in a matched set of well-characterized HPV-dependent and HPV-independent tonsillar tumors and equivalent immortalized keratinocyte clones to define potential and clinically relevant biomarkers of HNC of different etiology.
  
  
  
  Fresh frozen tonsillar cancer tissues were analyzed together with non-malignant tonsillar tissues and compared with cervical tumors and normal cervical tissues. Furthermore, relative miRNAs abundance levels of primary and immortalized human keratinocyte clones were evaluated. The global quantitation of miRNA gene abundance was performed using a TaqMan Low Density Array system. The confirmation of differentially expressed miRNAs was performed on a set of formalin-fixed paraffin-embedded tumor samples enriched for the tumor cell fraction by macrodissection.
  
  
  
  We defined 46 upregulated and 31 downregulated miRNAs characteristic for the HPV-positive tonsillar tumors and 42 upregulated miRNAs and 42 downregulated miRNAs characteristic for HPV-independent tumors. In comparison with the expression profiles in cervical tumors, we defined miR-141-3p, miR-15b-5p, miR-200a-3p, miR-302c-3p, and miR-9-5p as specific for HPV induced malignancies. MiR-335-5p, miR-579-3p, and miR-126-5p were shared by the expression profiles of HPV-positive tonsillar tumors and of the HPV immortalized keratinocyte clones, whereas miR-328-3p, miR-34c-3p, and miR-885-5p were shared by the miRNA profiles of HPV-negative tonsillar tumors and the HPV-negative keratinocytes.
  
  
  
  We identified the miRNAs characteristic for HPV-induced tumors and tonsillar tumors of different etiology, and the results were compared with those of the model system. Our report presents the basis for further investigations leading to the identification of clinically relevant diagnostic and/or therapeutic biomarkers for tumors of viral and non-viral etiology.
authors.affiliation: Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.|Department of Immunology, Institute of Hematology and Blood Transfusion, U Nemocnice 2094/1, Prague 2, CZ-12820, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Vojtechova
authors.affiliation: Department of Immunology, Institute of Hematology and Blood Transfusion, U Nemocnice 2094/1, Prague 2, CZ-12820, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Sabol
authors.affiliation: Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.|Department of Immunology, Institute of Hematology and Blood Transfusion, U Nemocnice 2094/1, Prague 2, CZ-12820, Czech Republic.
authors.forename: Martina
authors.initials: M
authors.lastname: Salakova
authors.affiliation: Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic.|Department of Immunology, Institute of Hematology and Blood Transfusion, U Nemocnice 2094/1, Prague 2, CZ-12820, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Smahelova
authors.affiliation: Molecular Mechanisms and Biomarkers Group, International Agency for Research on Cancer, Lyon, France.
authors.forename: Jiri
authors.initials: J
authors.lastname: Zavadil
authors.affiliation: Veterans Affairs Healthcare System and Department of Pathology, University of Iowa, Iowa City, IA, USA.
authors.forename: Lubomir
authors.initials: L
authors.lastname: Turek
authors.affiliation: Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Grega
authors.affiliation: Department of Otorhinolaryngology and Head and Neck Surgery, 1st Faculty of Medicine, Charles University in Prague, Motol University Hospital, Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Klozar
authors.affiliation: Department of Immunology, Institute of Hematology and Blood Transfusion, U Nemocnice 2094/1, Prague 2, CZ-12820, Czech Republic.
authors.forename: Bohumir
authors.initials: B
authors.lastname: Prochazka
authors.affiliation: Department of Genetics and Microbiology, Faculty of Science, Charles University in Prague, Prague, Czech Republic. rutach@uhkt.cz.|Department of Immunology, Institute of Hematology and Blood Transfusion, U Nemocnice 2094/1, Prague 2, CZ-12820, Czech Republic. rutach@uhkt.cz.
authors.forename: Ruth
authors.identifier: 0000-0001-7689-9727
authors.initials: R
authors.lastname: Tachezy
mesh_terms: D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D030361:Papillomavirus Infections / Q000235:genetics*; D025341:Principal Component Analysis; D014067:Tonsillar Neoplasms / Q000235:genetics* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology
chemical_list: D035683:MicroRNAs
keywords: Head and neck cancer; Human papillomavirus; Tonsillar tumor; miRNA