ArticleJournal of neuro-oncology2012
E-cadherin as a predictive marker of brain metastasis in non-small-cell lung cancer, and its regulation by pioglitazone in a preclinical model.
Article in Journal of neuro-oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- A Comprehensive Meta-Analysis of Association between EGFR Mutation Status and Brain Metastases in NSCLC.Pathology oncology research : POR · 2019Pooled it
- [Advances in diagnosis and treatment of brain metastases from the primary lung cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2013Pooled it
- Review
- Pioglitazone-Based Combination Approaches for Non-Small-Cell Lung Cancer.Pharmaceutics · 2025Review
- Breaking boundaries: role of the brain barriers in metastatic process.Fluids and barriers of the CNS · 2025Review
- Article
- A Review of the Molecular Determinants of Therapeutic Response in Non-Small Cell Lung Cancer Brain Metastases.International journal of molecular sciences · 2024Review
- The origin of brain malignancies at the blood-brain barrier.Cellular and molecular life sciences : CMLS · 2023Review
- Effect of BIM expression on the prognostic value of PD-L1 in advanced non-small cell lung cancer patients treated with EGFR-TKIs.Scientific reports · 2023Article
- The Journey of Cancer Cells to the Brain: Challenges and Opportunities.International journal of molecular sciences · 2023Review
- Brain metastases and lung cancer: molecular biology, natural history, prediction of response and efficacy of immunotherapy.Frontiers in immunology · 2023Review
- Whole-exome sequencing identifies somatic mutations associated with lung cancer metastasis to the brain.Annals of translational medicine · 2021Article
- Primary tumor and metastasis-sectioning the different steps of the metastatic cascade.Translational lung cancer research · 2020Review
- Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone.International journal of molecular sciences · 2020Article
- Advances in Lung Cancer Driver Genes Associated With Brain Metastasis.Frontiers in oncology · 2020Review
- Article
- Troglitazone inhibits the migration and invasion of PC-3 human prostate cancer cells by upregulating E-cadherin and glutathione peroxidase 3.Oncology letters · 2018Article
- E-Cadherin Loss Accelerates Tumor Progression and Metastasis in a Mouse Model of Lung Adenocarcinoma.American journal of respiratory cell and molecular biology · 2018Article
- Systemic Therapy of Lung Cancer CNS Metastases Using Molecularly Targeted Agents and Immune Checkpoint Inhibitors.CNS drugs · 2018Review
- Lung cancer-associated brain metastasis: Molecular mechanisms and therapeutic options.Cellular oncology (Dordrecht, Netherlands) · 2017Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 O(6)-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.
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Registered trials
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