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Molecular Characterization of Chronic Obstructive Pulmonary Disease-Related Non-Small Cell Lung Cancer Through Aberrant Methylation and Alterations of EGFR Signaling

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The aim of this study was to evaluate the molecular influence of chronic obstructive pulmonary diseases (COPD) on the pathogenesis of non-small cell lung cancer (NSCLC).

Materials and Methods

The methylation profiles of 12 genes, and the epidermal growth factor receptor (EGFR) and KRAS mutations were determined for samples from 229 NSCLC patients. In addition, protein expression of EGFR and HER2 in 116 NSCLCs was analyzed based on the presence or absence of COPD.

Results

IL-12Rβ2 and Wif-1 methylation and HER2 overexpression were more frequent events in the COPD group. Eighty nonmalignant lung tissues had no correlation with any molecular changes between the COPD and the non-COPD group. EGFR mutation was significantly higher in the non-COPD group, while EGFR expression was inversely correlated with %FEV1.0. In the COPD group, unmethylated SPARC and sFRP-2 genes or a negative CpG island methylator phenotype (CIMP) was a negative prognostic factor, while methylation of p16INK4A and WNT antagonist genes was a negative prognostic factor in the non-COPD group.

Conclusions

Novel characteristics of COPD-related NSCLC were identified by examination of methylation profiles and alterations of EGFR signaling. In consideration of the high sensitivity to smoking in patients with COPD, NSCLC with COPD might be a distinct population of smoke-related NSCLC, the genetic profile of which is quite different from non-COPD NSCLC.

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Authors and Affiliations

  1. Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan

    Makoto Suzuki MD, Hironobu Wada MD, Mitsuru Yoshino MD, Lei Tian MD, Hidemi Suzuki MD, Mahmoud Alaa MD, Hajime Tamura MD, Taiki Fujiwara MD, Kaoru Nagato MD, Shinichiro Motohashi MD, Yasumitsu Moriya MD, Hidehisa Hoshino MD, Shigetoshi Yoshida MD, Kiyoshi Shibuya MD & Ichiro Yoshino MD

  2. Department of Chest Surgery, NHO Okayama Medical Center, Okayama, Japan

    Hisayuki Shigematsu MD

  3. Department of Basic Pathology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Kenzo Hiroshima MD & Yukio Nakatani MD

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  1. Makoto Suzuki MD
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Correspondence to Makoto Suzuki MD.

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Suzuki, M., Wada, H., Yoshino, M. et al. Molecular Characterization of Chronic Obstructive Pulmonary Disease-Related Non-Small Cell Lung Cancer Through Aberrant Methylation and Alterations of EGFR Signaling. Ann Surg Oncol 17, 878–888 (2010). https://doi.org/10.1245/s10434-009-0739-3

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  • DOI: https://doi.org/10.1245/s10434-009-0739-3

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