Journal of Neuro-Oncology

, Volume 109, Issue 2, pp 219–227 | Cite as

E-cadherin as a predictive marker of brain metastasis in non-small-cell lung cancer, and its regulation by pioglitazone in a preclinical model

  • Jin Young Yoo
  • Seung-Ho Yang
  • Jung Eun Lee
  • Deog Gon Cho
  • Hoon Kyo Kim
  • Sung Hwan Kim
  • Il Sup Kim
  • Jae Taek Hong
  • Jae Hoon Sung
  • Byung Chul Son
  • Sang Won Lee
Laboratory Investigation


It remains unclear whether patients with non-small-cell lung cancer (NSCLC) develop brain metastasis during or after standard therapy. We attempted to identify biological markers that predict brain metastasis, and investigated how to modulate expression of such markers. A case–control study of patients who were newly diagnosed with NSCLC and who had developed brain metastasis during follow-up was conducted between 2004 and 2009. These patients were compared with a control group of patients who had NSCLC but no evidence of brain metastasis. Immunohistochemical analysis of expression of Ki-67, p53, Bcl-2, Bax, vascular endothelial growth factor, epidermal growth factor receptor, caspase-3, and E-cadherin was conducted. The methylation status of the genes for O6-methylguanine-DNA-methyltransferase, tissue inhibitor of matrix metalloproteinase (TIMP)-2, TIMP-3, and death-associated protein-kinase was also determined, by use of a methylation-specific polymerase chain reaction. A significantly increased risk of developing brain metastasis was associated with the presence of primary tumors with low E-cadherin expression in patients with NSCLC. We also investigated the effects of pioglitazone, a peroxisome proliferator-activated receptor γ-activating drug, in tumor-bearing mouse models. We found that E-cadherin expression was proportional to pioglitazone exposure time. Interestingly, pioglitazone pretreatment before cancer cell inoculation prevented loss of E-cadherin expression and reduced expression of MMP9 and fibronectin, compared with the control group. E-cadherin expression could be a predictor of brain metastasis in patients with NSCLC. Preventive treatment with pioglitazone may be useful for modulating E-cadherin expression.


Biomarker Brain metastasis NSCLC PPARγ Prevention E-cadherin 



This work was supported by a National Research Foundation of Korea Grant funded by the Korean Government (2009-0069346). We thank Se Hoon Kim for the analysis of in-vivo experiments.

Supplementary material

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Supplementary material 1 (DOC 5929 kb)
11060_2012_890_MOESM2_ESM.doc (15 kb)
Supplementary material 2 (DOC 15 kb)


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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Jin Young Yoo
    • 1
  • Seung-Ho Yang
    • 2
  • Jung Eun Lee
    • 2
  • Deog Gon Cho
    • 3
  • Hoon Kyo Kim
    • 4
  • Sung Hwan Kim
    • 5
  • Il Sup Kim
    • 2
  • Jae Taek Hong
    • 2
  • Jae Hoon Sung
    • 2
  • Byung Chul Son
    • 2
  • Sang Won Lee
    • 2
  1. 1.Department of PathologySt. Vincent’s Hospital, The Catholic University of KoreaPaldal-guKorea
  2. 2.Department of NeurosurgerySt. Vincent’s Hospital, The Catholic University of KoreaPaldal-guKorea
  3. 3.Department of Thoracic SurgerySt. Vincent’s Hospital, The Catholic University of KoreaPaldal-guKorea
  4. 4.Department of Internal MedicineSt. Vincent’s Hospital, The Catholic University of KoreaPaldal-guKorea
  5. 5.Department of Radiation OncologySt. Vincent’s Hospital, The Catholic University of KoreaPaldal-guKorea

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