Epstein-Barr virus microRNAs and lung cancer

J. Koshiol, M. L. Gulley, Y. Zhao, M. Rubagotti, F. M. Marincola, M. Rotunno, W. Tang, A. W. Bergen, P. A. Bertazzi, D. Roy, A. C. Pesatori, I. Linnoila, D. Dittmer, A. M. Goldstein, N. E. Caporaso, L. M. McShane, E. Wang, M. T. Landi

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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.Conclusion: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.

Original languageEnglish
Pages (from-to)320-326
Number of pages7
JournalBritish Journal of Cancer
Volume105
Issue number2
DOIs
Publication statusPublished - 12 Jul 2011
Externally publishedYes

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Keywords

  • Epstein-Barr virus
  • lung cancer
  • microarray
  • microRNA
  • qPCR

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Koshiol, J., Gulley, M. L., Zhao, Y., Rubagotti, M., Marincola, F. M., Rotunno, M., Tang, W., Bergen, A. W., Bertazzi, P. A., Roy, D., Pesatori, A. C., Linnoila, I., Dittmer, D., Goldstein, A. M., Caporaso, N. E., McShane, L. M., Wang, E., & Landi, M. T. (2011). Epstein-Barr virus microRNAs and lung cancer. British Journal of Cancer, 105(2), 320-326. https://doi.org/10.1038/bjc.2011.221