Imbalance in redox status is associated with tumor aggressiveness and poor outcome in lung adenocarcinoma patients

Purpose The expression levels of human antioxidant genes (HAGs) and oxidative markers were investigated in light of lung adenocarcinoma aggressiveness and patient outcome. Methods We assayed in vitro the tumoral invasiveness and multidrug resistance in human lung adenocarcinoma (AdC) cell lines (EKV...

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Bibliographic Details
Published in:Journal of cancer research and clinical oncology 2014-03, Vol.140 (3), p.461-470
Main Authors: Lisbôa da Motta, Leonardo, Müller, Carolina B., De Bastiani, Marco A., Behr, Guilherme A., França, Fernanda S., da Rocha, Ricardo F., Minotto, Juliane B., Meurer, Rosalva T., Fernandes, Marilda C., Roehe, Adriana, Markoski, Melissa M., Andrade, Cristiano F., Castro, Mauro A. A., Klamt, Fábio
Format: Article
Language:English
Subjects:
Adenocarcinoma - drug therapy
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Adenocarcinoma of Lung
Adult
Aged
Aldehydes - metabolism
Antioxidants - metabolism
Biomarkers
Cancer Research
Cell Line, Tumor
Cellular biology
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Female
Gene expression
Gene Expression Regulation, Neoplastic
Hematology
Humans
Immunohistochemistry
Internal Medicine
Lipid Peroxidation
Lung cancer
Lung Neoplasms - drug therapy
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Male
Medicine
Medicine & Public Health
Microarray Analysis
Middle Aged
Multivariate Analysis
Neoplasm Invasiveness
Neoplasm Staging
Odds Ratio
Oncology
Original Paper
Oxidation-Reduction
Oxidative stress
Predictive Value of Tests
Prognosis
Proportional Hazards Models
Retrospective Studies
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Summary:Purpose The expression levels of human antioxidant genes (HAGs) and oxidative markers were investigated in light of lung adenocarcinoma aggressiveness and patient outcome. Methods 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. Results 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  
ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-014-1586-6