title: Potentially prognostic miRNAs in HPV-associated oropharyngeal carcinoma.
abstract: OBJECTIVE
  Deregulation of miRNAs is associated with almost all human malignancies. Human papillomavirus (HPV)-associated oropharyngeal carcinoma (OPC) has a significantly more favorable outcome compared with HPV-negative OPCs; however, the underlying mechanisms are not well understood. Hence, the objectives of this study were to determine whether miRNA expression differed as a function of HPV status and to assess whether such miRNAs provide prognostic value beyond HPV status.
  
  
  METHODS
  Global miRNA profilings were conducted on 88 formalin-fixed and paraffin-embedded (FFPE) OPC biopsies (p16-positive: 56; p16-negative: 32), wherein the expression levels of 365 miRNAs plus 3 endogenous controls were simultaneously measured using quantitative real-time (qRT)-PCR. Seven FFPE specimens of histologically normal tonsils were used as controls.
  
  
  RESULTS
  Overall, 224 miRNAs were expressed in more than 80% of the investigated samples, with 128 (57%) being significantly differentially expressed between tumor versus normal tissues (P < 0.05). Upregulated miR-20b, miR-9, and miR-9* were significantly associated with HPV/p16-status. Three miRNA sets were significantly associated with overall survival (miR-107, miR-151, miR-492; P = 0.0002), disease-free survival (miR-20b, miR-107, miR-151, miR-182, miR-361; P = 0.0001), and distant metastasis (miR-151, miR-152, miR-324-5p, miR-361, miR492; P = 0.0087), which retained significance even after adjusting for p16 status. The associated biologic functions of these miRNAs include immune surveillance, treatment resistance, invasion, and metastasis.
  
  
  CONCLUSIONS
  We have identified several miRNAs, which associate with HPV status in OPC; furthermore, three candidate prognostic sets of miRNAs seem to correlate with clinical outcome, independent of p16 status. Furthermore, evaluations will offer biologic insights into the mechanisms underlying the differences between HPV-positive versus HPV-negative OPC.
authors: Ontario Cancer Institute, University Health Network, Toronto, Ontario, Canada.
authors: Angela B Y
authors: AB
authors: Hui
authors: Alice
authors: A
authors: Lin
authors: Wei
authors: W
authors: Xu
authors: Levi
authors: L
authors: Waldron
authors: Bayardo
authors: B
authors: Perez-Ordonez
authors: Ilan
authors: I
authors: Weinreb
authors: Wei
authors: W
authors: Shi
authors: Jeff
authors: J
authors: Bruce
authors: Shao Hui
authors: SH
authors: Huang
authors: Brian
authors: B
authors: O'Sullivan
authors: John
authors: J
authors: Waldron
authors: Patrick
authors: P
authors: Gullane
authors: Jonathan C
authors: JC
authors: Irish
authors: Kelvin
authors: K
authors: Chan
authors: Fei-Fei
authors: FF
authors: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D054884:Host-Pathogen Interactions; D052162:Human papillomavirus 16 / Q000235:genetics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009959:Oropharyngeal Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics* / Q000502:physiology; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics* / Q000821:virology; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; C534451:MIRN20a microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs