Clinical Significance Of Epithelial-mesenchymal Transition-related Protein Expressions In The Carcinoma Cells Of Non-small Cell Lung Cancer

Objective:Lung cancer is the malignant tumor with highest morbidity and mortality in the world. More than80%of lung cancer is non-small cell lung cancer (NSCLC). The surgical resection is still the most effective method for treatment of NSCLC, but many patients need the chemotherapy because the surgery chance is lost when the cancers diagnosed have infiltrated diffusely and metastasized distantly. Moreover, the patients often need the adjuvant chemotherapy even though they have received surgical treatment. However, chemotherapy lacks specificity for the cancer and often has many side effects on patients. Recently, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) has succeeded in treatment of NSCLC and received more and more attention. However, a lot of patients can not get benefit from the EGFR-TKI because of primary and secondary drug resistances of the cancer. Epithelial-mesenchymal transition (EMT) is one of the important mechanisms of drug resistance. It would have a certain significance to understand the original EMT status of the cancer cells for assessment of the effect of the EGFR-TKI.E-cadherin is an essential protein to maintain the stability of epithelial cells. If the protein expression decreased, the adhesions among the epithelial cells would become weak. The cells could escape from primary area, pass though the basement membrane and invade to the stroma. Vimentin is an intermediate fiber protein, which does not express in the epithelial cells. The vimentin expression in the cancer cells indicates that the cells have transformed to mesenchymal phenotype from epithelial phenotype. Decreasing expression of E-cadherin and increasing expression of vimentin have been supposed to the makers of the occurrence of EMT. Slug is one of the transcription factors regulating the EMT. Slug can recognize and bind to E-box elements in the proximal E-cadherin promoter, and then repress expression of the E-cadherin protein to promote the EMT. In order to investigate the EMT status of the cancer cells before EGFR-TKI treatment, we detect the expressions of E-cadherin, vimentin and slug protein in the cancer cells and the bronchus epithelia surrounding tumor cells. We hope to provide some assistance for application of EGFR-TKI treatment to NSCLC.Methods:The samples of NSCLC and their surrounding tissues were collected from the Affiliated Hospital of Dalian Medical University. The immunohistochemistry was used to detect expressions of E-cadherin, vimentin and slug protein in147samples of NSCLC and44samples of bronchus epithelia surrounding tumor. The SPSS17.0statistic software was used to analyze the correlations of these protein expressions to clinicopathological agents (gender, age, smoking history, histological type, differentiation, lymph node metastasis) as well as the relationship among these protein expressions.Results:The positive expression rate of E-cadherin protein in the tumor cells of NSCLC was significantly lower than that in bronchus epithelia surrounding tumor cells (53.7%vs70.5%, P<0.05). The rate in the male patients was significantly lower than that in the female (44.0%vs66.7%, P<0.05). The rate in the smoking patients was significantly lower than that in the non-smoking patients (42.9%vs60.4%, P<0.05) The rate in the poorly differentiated adenocarcinoma was significantly lower than that in the well-moderately differentiated adenocarcinoma (41.2%vs63.9%, P<0.05) However, the expression was not significantly related to age of patients and tumor histological type, lymph node metastasis (P>0.05)The positive expression rate of vimentin protein in the tumor cells of NSCLC was significantly higher than that in bronchus epithelia surrounding tumor cells (37.4%vs20.5%, P<0.05). The rate in the poorly differentiated adenocarcinoma was significantly higher than that in the well-moderately differentiated adenocarcinoma(55.9%vs34.4%, P<0.05). The expression was not significantly related to gender, age, smoking status of patients and tumor histological type, lymph node metastasis (P>0.05)The positive expression rate of slug protein in the tumor cells of NSCLC was significantly higher than that in bronchus epithelia surrounding tumor cells (52.4%vs31.8%, P<0.05). The rate in the adenocarcinoma was significantly higher than that in the squamous carcinoma (58.9%vs40.4%, P<0.05). The expression was not significantly related to gender, age, smoking status of patients and differentiation, lymph node metastasis (P>0.05)In the tumor cells of NSCLC, the expression of E-cadherin protein was negatively correlated to that of slug (r=-0.244, P<0.05), but the expression of vimentin protein was not correlated to that of slug (r=0.146, P>0.05). The expression of vimentin was not correlated to that of E-cadherin (r=0.087, P>0.05)Conclusions:1. EMT phenomenon occurred in the development of NSCLC.2. Transcription factor-slug could repress the expression of E-cadherin protein to promote the EMT.3. The well-differentiated adenocarcinoma from female patients which was sensitive to EGFR-TKI would express E-cadherin.4. It would be helpful to detect the EMT status of the cancer cells for us to understand the sensitivity of patients to EGFR-TKI before the molecular targeting therapy.