Imbalance in redox status is associated with tumor aggressiveness and poor outcome in lung adenocarcinoma patients
Autor: | Leonardo Lisbôa da Motta, Fernanda Stapenhorst França, Marilda da Cruz Fernandes, Carolina Beatriz Müller, Mauro A. A. Castro, Adriana Vial Roehe, Juliane Borba Minotto, Guilherme Antônio Behr, Ricardo Fagundes da Rocha, Cristiano Feijó Andrade, Melissa Medeiros Markoski, Rosalva Thereza Meurer, Marco Antônio De Bastiani, Fábio Klamt |
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Rok vydání: | 2013 |
Předmět: |
Oncology
Adult Male Cancer Research medicine.medical_specialty Lung Neoplasms Microarray Adenocarcinoma of Lung Adenocarcinoma medicine.disease_cause Antioxidants Predictive Value of Tests Internal medicine Cell Line Tumor medicine Odds Ratio Humans Neoplasm Invasiveness Lung cancer Survival rate Aged Neoplasm Staging Proportional Hazards Models Retrospective Studies Aldehydes Microarray analysis techniques business.industry General Medicine Middle Aged medicine.disease Microarray Analysis Prognosis Immunohistochemistry Drug Resistance Multiple Gene Expression Regulation Neoplastic Tumor progression Drug Resistance Neoplasm Multivariate Analysis Female Lipid Peroxidation business Oxidation-Reduction Oxidative stress |
Zdroj: | Journal of cancer research and clinical oncology. 140(3) |
ISSN: | 1432-1335 |
Popis: | The expression levels of human antioxidant genes (HAGs) and oxidative markers were investigated in light of lung adenocarcinoma aggressiveness and patient outcome. We assayed in vitro the tumoral invasiveness and multidrug resistance in human lung adenocarcinoma (AdC) cell lines (EKVX and A549). Data were associated with several redox parameters and differential expression levels of HAG network. The clinicopathological significance of these findings was investigated using microarray analysis of tumor tissue and by immunohistochemistry in archival collection of biopsies. An overall increased activity (expression) of selected HAG components in the most aggressive cell line (EKVX cells) was observed by bootstrap and gene set enrichment analysis (GSEA). In vitro validation of oxidative markers revealed that EKVX cells had high levels of oxidative stress markers. In AdC cohorts, GSEA of microarray datasets showed significantly high levels of HAG components in lung AdC samples in comparison with normal tissue, in advanced stage compared with early stage and in patients with poor outcome. Cox multivariate regression analysis in a cohort of early pathologic (p)-stage of AdC cases showed that patients with moderate levels of 4-hydroxynonenal, a specific and stable end product of lipid peroxidation, had a significantly less survival rate (hazard ratio of 8.87) (P |
Databáze: | OpenAIRE |
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