Expression And Prognostic Significance Of Epithelial-mesenchymal Transition-related Proteins In Non-small Cell Lung Cancer

Lung cancer is one of the most common cancers in the world, of which the incidence is ascending year by year, and the mortality is at the first place in all malignant tumors. Non-small cell lung cancer(NSCLC) accounts for 85% of lung cancer. Nowdays, the treatment of lung cancer including surgery, chemotherapy and radiation therapy, but the therapeutic effect is still unsatisfactory. The leading deaths of lung cancer patients is recurrence and metastasis. Epithelial-mesenchymal transition(EMT) is defined as switching of polarized epithelial cells to a migratory fibroblastoid phenotype. EMT is considered to be one of the major molecular mechanisms inducing tumor invasion and metastasis. This transition involves loss or redistribution of tight- and adherence junction proteins like the E-cadherin,β-catenin and a switch to the expression of mesenchymal proteins like the Snail, Vimentin which confer upon cells the ability to pass through the basement membrance. This aim of this study was to evaluate the prognostic value of EMT-related proteins E-cadherin andβ-catenin, Snail, Vimentin expression in patients with NSCLCMethods1. The studied series consisted of formalin-fixed-paraffin-embedded tissue samples from 165 patients diagnosed with NSCLC. Samples were obtains from 115 male and 50 female. The mean patient age was 65 yeas. There were 107 cases of adenocarcinoma and 58 cases of squamous cell carcinoma, and 64 stageⅠ,107 stageⅡ-Ⅳ. All patients were followed up and had detailed data.2. To investigate the accumulative effects of E-cadherin/β-catenin complex, Snail, Vimentin expression on the prognosis of NSCLC, we divided these 165 patients into four groups according to the number of the changed markers: group 1(none changed), group 2(one changed), group 3(two changed), group 4(three changed). Then we divided the patients into the following two groups: EMT-L1(group 1 and group 2), EMT-L2(group 3 and group 4)3. The tissue microarry(TMA) technique and immunohistochemistry stain were used to detect the expression of E-cadherin,β-catenin, Snail, Vimentin proteins in 165 NSCLC. The association between E-cadherin,β-catenin, Snail, Vimentin expression and patients'overall and prognostic was investigated.Results1. Loss of epithelial protein and/or acquisition of the expression of mesenchymal proteins were observed in non-small cell lung cancer. The membranous expression in tumor cells of E-cadherin orβ-cateninl was showed in 66.7%, 50.9%. The nuclear expression in tumor cells of Snail was showed in 45.5%. The cytoplasmic expression in tumor cells of Vimentin was showed in 33.9%. An inverse correlation was observed for Snail expression and E-cadherin protein levels(P<0.001), and the loss of E-cadherin was significantly associated withβ-catenin losing(P=0.003).2. The alterations of Snail was found to be significantly related to histological differentiation(P=0.013). Vimentin was found to be significantly related to venous invasion(P=0.046). The alterations in the expression of E-cadherin/β-catenin complex, Snail, Vimentin was associated with a shorter overall survival (P=0.0025, P=0.0059, P=0.0257).3. Subjects were divided into two groups according to degree of EMT-related protein altertation. Co-alteration of more than two EMT-related proteins were found to be significantly associated with poorly differentiated histology(P=0.003) and unfavourable outcome(P<0.0001). Multivariate analysis showed that alterations in the expression of EMT-ralated proteins were independently associated with poor prognosis.Conclusions1. The loss of epithelial markers E-cadherin andβ-catenin has been find in some paitents,. Some patients also find the overpression of Snail, Vimentin. The EMT process may be an important molecular event during the progression of NSCLC.2. The overpression of Snail is associated with poorly differentiated histology. It showed that Snail may have an important function on the cell's differentiation. The overpression of Vimentin is associated with venous invasion. The overpression of Vimentin make the tumor cell too easy to invase venous.3. The results show that loss of epithelial proteins and/or the acquisition of mesenchymal proteins are associated with poor outcome in non-small cell lung cancer. The alterations in the expression of any two or all of E-cadherin/β-catenin complex, Snail, Vimentin is a significant prognostic marker to predict overall in patients with respectable NSCLC. The information generated will be valuable for the prognosis and management of patients with NSCLC.