Aberrant methylation of CXCL12 in non-small cell lung cancer is associated with an unfavorable prognosis

Corrigendum in: /ijo/47/2/791

  • Authors:
    • Makoto Suzuki
    • Sherif Mohamed
    • Takahiro Nakajima
    • Rieko Kubo
    • Lei Tian
    • Taiki Fujiwara
    • Hidemi Suzuki
    • Kaoru Nagato
    • Masako Chiyo
    • Shinichiro Motohashi
    • Kazuhiro Yasufuku
    • Akira Iyoda
    • Shigetoshi Yoshida
    • Yasuo Sekine
    • Kiyoshi Shibuya
    • Kenzo Hiroshima
    • Yukio Nakatani
    • Ichiro Yoshino
    • Takehiko Fujisawa
  • View Affiliations

  • Published online on: July 1, 2008     https://doi.org/10.3892/ijo.33.1.113
  • Pages: 113-119
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Abstract

Chemokines play an important role in the pathogenesis of non-small cell lung cancer (NSCLC). However, aberrant methylation of CXCL12 has not been examined in NSCLC. CXCL12 mRNA expression and methylation were examined in 17 NSCLC cell lines by RT-PCR and methylation-specific PCR (MSP). MSP was performed on 236 tumor specimens from NSCLC patients who received curative intent surgery. CXCL12 and CXCR4 protein expression was examined in 90 of the 236 NSCLC specimens by immunohistochemistry. Down-regulation of CXCL12 expression was found in 10 of 17 (59%) NSCLC cell lines compared with normal bronchial cells. Treatment of 8 expression-negative cell lines with a demethylating agent restored expression in all cases. Twelve cell lines (71%) showed aberrant methylation, and good concordance between methylation and expression was present. Aberrant methylation occurred in 85 out of 236 (36%) primary NSCLCs in a tumor-specific manner. In multivariate analysis, CXCL12 methylation correlated strongly and independently with prognosis both in all patients with NSCLCs and in those with stage I NSCLCs (hazard ratio=1.68, P=0.015 and hazard ratio=3.58, P=0.017). Secreted protein CXCL12 and its receptor CXCR4 were abundant in NSCLC cells (72 out of 90, 80%; 57 out of 90, 63%) and correlated with the progression of NSCLCs. In conclusion, epigenetic silencing of CXCL12 is a frequent event in NSCLCs, and could be an independent and powerful prognostic marker in patients with NSCLCs and those with stage I disease. Analysis for CXCL12 may provide novel opportunities for prognosis and therapy of resected NSCLCs.

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July 2008
Volume 33 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Suzuki M, Mohamed S, Nakajima T, Kubo R, Tian L, Fujiwara T, Suzuki H, Nagato K, Chiyo M, Motohashi S, Motohashi S, et al: Aberrant methylation of CXCL12 in non-small cell lung cancer is associated with an unfavorable prognosis Corrigendum in /ijo/47/2/791. Int J Oncol 33: 113-119, 2008
APA
Suzuki, M., Mohamed, S., Nakajima, T., Kubo, R., Tian, L., Fujiwara, T. ... Fujisawa, T. (2008). Aberrant methylation of CXCL12 in non-small cell lung cancer is associated with an unfavorable prognosis Corrigendum in /ijo/47/2/791. International Journal of Oncology, 33, 113-119. https://doi.org/10.3892/ijo.33.1.113
MLA
Suzuki, M., Mohamed, S., Nakajima, T., Kubo, R., Tian, L., Fujiwara, T., Suzuki, H., Nagato, K., Chiyo, M., Motohashi, S., Yasufuku, K., Iyoda, A., Yoshida, S., Sekine, Y., Shibuya, K., Hiroshima, K., Nakatani, Y., Yoshino, I., Fujisawa, T."Aberrant methylation of CXCL12 in non-small cell lung cancer is associated with an unfavorable prognosis Corrigendum in /ijo/47/2/791". International Journal of Oncology 33.1 (2008): 113-119.
Chicago
Suzuki, M., Mohamed, S., Nakajima, T., Kubo, R., Tian, L., Fujiwara, T., Suzuki, H., Nagato, K., Chiyo, M., Motohashi, S., Yasufuku, K., Iyoda, A., Yoshida, S., Sekine, Y., Shibuya, K., Hiroshima, K., Nakatani, Y., Yoshino, I., Fujisawa, T."Aberrant methylation of CXCL12 in non-small cell lung cancer is associated with an unfavorable prognosis Corrigendum in /ijo/47/2/791". International Journal of Oncology 33, no. 1 (2008): 113-119. https://doi.org/10.3892/ijo.33.1.113