title: Epstein-Barr virus microRNAs and lung cancer.
abstract: BACKGROUND
  We conducted the first analysis of viral microRNAs (miRNAs) in lung cancer, with a focus on Epstein-Barr virus (EBV).
  
  
  METHODS
  We evaluated viral miRs with a two-channel oligo-array targeting mature, anti-sense miRNAs in 290 cases. In 48 cases, we compared microarray and real-time quantitative PCR (qPCR) expression for three EBV miRNAs. We tested for EBV DNA, RNA, and protein in tumour tissue from six cases with and six cases without strong qPCR-based evidence of EBV miRNAs.
  
  
  RESULTS
  The EBV miRNAs strongly differentiated between adenocarcinoma and squamous cell carcinoma using the microarray (P<0.01 for 9 out of 16 EBV miRNAs). However, microarray and qPCR measurements of BART1, BART2, and BHRF1-3 expression were not significantly correlated (P=0.53, 0.94, and 0.47, respectively). Although qPCR provided substantial evidence of EBV miRNAs in 7 out of 48 cases, only 1 of these 7 cases had detectable EBV DNA in tumour tissue. None had detectable EBV RNA or protein by histochemical stains.
  
  
  CONCLUSIONS
  In a comprehensive evaluation of EBV miRNA, DNA, RNA, and protein in lung cancer, we found little evidence of EBV in lung tumour tissue. Discrepancies between microarray- and qPCR-based strategies highlight the difficulty of validating molecular markers of disease. Our results do not support a role of EBV in lung cancer.
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. koshiolj@mail.nih.gov
authors.forename: J
authors.initials: J
authors.lastname: Koshiol
authors.forename: M L
authors.initials: ML
authors.lastname: Gulley
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: M
authors.initials: M
authors.lastname: Rubagotti
authors.forename: F M
authors.initials: FM
authors.lastname: Marincola
authors.forename: M
authors.initials: M
authors.lastname: Rotunno
authors.forename: W
authors.initials: W
authors.lastname: Tang
authors.forename: A W
authors.initials: AW
authors.lastname: Bergen
authors.forename: P A
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: D
authors.initials: D
authors.lastname: Roy
authors.forename: A C
authors.initials: AC
authors.lastname: Pesatori
authors.forename: I
authors.initials: I
authors.lastname: Linnoila
authors.forename: D
authors.initials: D
authors.lastname: Dittmer
authors.forename: A M
authors.initials: AM
authors.lastname: Goldstein
authors.forename: N E
authors.initials: NE
authors.lastname: Caporaso
authors.forename: L M
authors.initials: LM
authors.lastname: McShane
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: M T
authors.initials: MT
authors.lastname: Landi
mesh_terms: D000230:Adenocarcinoma / Q000150:complications / Q000235:genetics / Q000821:virology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000235:genetics / Q000821:virology*; D016022:Case-Control Studies; D004279:DNA, Viral / Q000032:analysis; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000235:genetics / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications / Q000235:genetics / Q000821:virology*; D008297:Male; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D046228:Microarray Analysis; D008875:Middle Aged; D012367:RNA, Viral / Q000032:analysis; D014764:Viral Proteins / Q000032:analysis
chemical_list: D004279:DNA, Viral; D035683:MicroRNAs; D012367:RNA, Viral; D014764:Viral Proteins