Expression profiles of thioredoxin family proteins in human lung cancer tissue: correlation with proliferation and differentiation

Aims: Lung cancer is one of the most common causes of cancer lethality worldwide. Despite recent progress, long-term survival remains poor. The aim of this study was to explore the expression pattern of the thioredoxin superfamily of proteins as potential new diagnostic and/or predictive markers. Methods and results: The expression of thioredoxin 1 (Trx1), thioredoxin reductase 1 (TrxR1), the isoforms TrxR1-v.2,3,5, glutaredoxin 1 (Grx1) and glutaredoxin 2 (Grx2) was examined by immunohistochemistry on paraffin-embedded sections from 42 cases of non-small cell lung cancer patients. Additional cases of lung cancer from tissue microarray were examined and the immunoreactivity was compared. All proteins except TrxR1 showed a significant correlation with the degree of differentiation in adenocarcinoma. Trx1 and TrxR1-v.2,3,5 also showed a significant correlation with differentiation in squamous carcinoma. Furthermore, Grx1 and Grx2 showed a clear inverse correlation with proliferation. The proliferation rate was further analysed in vitro in stably transfected Grx2 overproducing cells, showing that the proliferative effect of Grx2 is strictly dependent on subcellular localization. Conclusions: The thioredoxin family of proteins is important for growth and differentiation of lung cancer cells. The correlation with differentiation and proliferation of these enzymes makes them promising predictive/diagnostic markers.