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
Rok vydání: 2013
Předmět:
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