Low Expression of the FoxO4 Gene may Contribute to the Phenomenon of EMT in Non-small Cell Lung Cancer

Abstract

Because of its importance in tumor invasion and metastasis, the epithelial-mesenchymal transition (EMT)has become a research focus in the field of cancer. Recently, evidence has been presented that FoxO4 might beinvolved in EMT. Our study aimed to detect the expression of FoxO4, E-cadherin and vimentin in non-small celllung cancers (NSCLCs). We also investigated clinical features and their correlations with the markers. In ourstudy, FoxO4, E-cadherin and vimentin were assessed by immunohistochemistry in a tissue microarray (TMA)containing 150 cases of NSCLC. In addition, the expression level of FoxO4 protein was determined by Westernblotting. The percentages of FoxO4, E-cadherin and vimentin positive expression in NSCLCs were 42.7%,38.7% and 55.3%, respectively. Immunoreactivity of FoxO4 was low in NSCLC when compared with pairednormal lung tissues. There were significant correlations between FoxO4 and TNM stage (P<0.001), histologicaldifferentiation (P=0.004) and lymph node metastasis (P<0.001), but no significant links with age (P=0.323), gender(P=0.410), tumor size (P=0.084), smoking status (P=0.721) and histological type (P=0.281). Our study showedthat low expression of FoxO4 correlated with decreased expression of E-cadherin and elevated expression ofvimentin. Cox regression analysis indicated FoxO4 to be an independent prognostic factor in NSCLC (P=0.046).These data suggested that FoxO4 might inhibit the process of EMT in NSCLC, and might therefore be a targetfor therapy.