Hypoxia Induced High Expression of Thioredoxin Interacting Protein (TXNIP) in Non-small Cell Lung Cancer and its Prognostic Effect

Although associations between thioredoxin interacting protein (TXNIP) and cancers have been recognized,the effects of TXNIP on non-small cell lung cancer (NSCLC) prognosis remained to be determined in detail. Inaddition, while hypoxia is a key characteristic of tumor cell growth microenvironment, the effect of hypoxia onTXNIP expression is controversial. In this study, formaldehyde fixed and paraffin embedded (FFPE) samplesof 70 NSCLC patients who underwent resection between January 2010 and December 2011 were obtained.Evaluation of TXNIP and hypoxia inducible factor-1α (HIF-1α) protein expression in FFPE samples was madeby immunohistochemistry. By Kaplan-Meier method, patients with high TXNIP expression demonstrated asignificantly shorter progression free survival (PFS) compared with those with low TXNIP expression (18.0months, 95%CI: 11.7, 24.3 versus 23.0 months, 95%CI: 17.6, 28.4, P=0.02). High TXNIP expression level wasalso identified as an independent prognostic factor by Cox regression analysis (adjusted hazard ratio: 2.46;95%CI: 1.08, 5.56; P=0.03). Furthermore, TXNIP expression was found to be significantly correlated with HIF-1α expression (Spearman correlation=0.67, P=0.000). To further confirm correlations, we established a tumorcell hypoxic culture model. Expression of TXNIP was up-regulated in all three NSCLC cell lines (A549, SPC-A1,and H1299) under hypoxic conditions. This study suggests that hypoxia induces increased TXNIP expression inNSCLC and high TXNIP expression could be a poor prognostic marker.