Open Access

Aberrant methylation and silencing of IRF8 expression in non‑small cell lung cancer

  • Authors:
    • Makoto Suzuki
    • Koei Ikeda
    • Kenji Shiraishi
    • Ayami Eguchi
    • Takeshi Mori
    • Kentaro  Yoshimoto
    • Hidekatsu Shibata
    • Takaaki Ito
    • Yoshifumi Baba
    • Hideo Baba
  • View Affiliations

  • Published online on: June 11, 2014     https://doi.org/10.3892/ol.2014.2234
  • Pages: 1025-1030
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Abstract

The aim of the present study was to investigate the aberrant methylation and altered expression of the interferon regulatory factor 8 (IRF8) gene in non‑small cell lung cancer (NSCLC). Pyrosequencing assays were performed on 191 tumor specimens from NSCLC patients. The changes in IRF8 mRNA expression, prior to and following treatment with a demethylating agent and methylation itself, were examined in 13 lung cancer cell lines by quantitative polymerase chain reaction (qPCR) and pyrosequencing. IRF8 protein expression was examined in 94 of the 191 NSCLC specimens by immunohistochemical analysis. The IRF8 methylation level was significantly higher in the tumor tissues than in matched non‑malignant lung tissues (P<0.0001). IRF8 was more frequently methylated in tumor tissues compared with matched non‑malignant lung tissues, as defined by a predetermined cut‑off value (P<0.0001). The IRF8 methylation level was strongly correlated with the change in mRNA expression in lung cancer cell lines and with the protein expression level in primary tumors. The IRF8 gene was more frequently methylated in patients without an epidermal growth factor receptor (EGFR) mutation than in patients with an EGFR mutation (P=0.015). IRF8 methylation correlated with recurrent prognosis in adenocarcinomas (log‑rank test, P=0.048). IRF8 protein expression was frequently silenced in males, smokers, patients with non‑adenocarcinoma or with wild‑type EGFR, or in an advanced stage. IRF8 is often silenced by its methylation, which is a frequent event in NSCLC and, therefore, methylation of IRF8 may act as a prognostic marker for recurrence. Analysis of IRF8 methylation status may provide novel opportunities for improved prognosis and therapy of resected NSCLC.
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September-2014
Volume 8 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Suzuki M, Ikeda K, Shiraishi K, Eguchi A, Mori T, Yoshimoto K, Shibata H, Ito T, Baba Y, Baba H, Baba H, et al: Aberrant methylation and silencing of IRF8 expression in non‑small cell lung cancer. Oncol Lett 8: 1025-1030, 2014
APA
Suzuki, M., Ikeda, K., Shiraishi, K., Eguchi, A., Mori, T., Yoshimoto, K. ... Baba, H. (2014). Aberrant methylation and silencing of IRF8 expression in non‑small cell lung cancer. Oncology Letters, 8, 1025-1030. https://doi.org/10.3892/ol.2014.2234
MLA
Suzuki, M., Ikeda, K., Shiraishi, K., Eguchi, A., Mori, T., Yoshimoto, K., Shibata, H., Ito, T., Baba, Y., Baba, H."Aberrant methylation and silencing of IRF8 expression in non‑small cell lung cancer". Oncology Letters 8.3 (2014): 1025-1030.
Chicago
Suzuki, M., Ikeda, K., Shiraishi, K., Eguchi, A., Mori, T., Yoshimoto, K., Shibata, H., Ito, T., Baba, Y., Baba, H."Aberrant methylation and silencing of IRF8 expression in non‑small cell lung cancer". Oncology Letters 8, no. 3 (2014): 1025-1030. https://doi.org/10.3892/ol.2014.2234