| Background At present, lung cancer is the most malignant tumor in the world, among which non-small-cell lung cancer(NSCLC) accounts for the majority of lung cancer. The metastasis is closely related to the high mortality of lung cancer. Metastasis of lung cancer is an extremely complex multi-stage and multi-step process of multiple gene regulation. Epithelial mesenchymal transition(EMT) plays an important role in invasion and metastasis of malignant tumors, and is the key step in tumor invasion and metastasis. Cell adhesion is a very important step. Epithelial cadherin is a Ca2+-dependent transmembrane protein which can promote epithelial cells adhered to each other, maintain the integrity of the organizational structure. The expression of E-cadherin can inhibit tumor metastasis, but when the expression decrease or absence of E-cadherin may promote the metastasis of tumor cells. Studies have confirmed that E-cadherin is low expression in tumor tissue, especially in the presence of lymph node metastasis or low differentiation of E-cadherin expression in lung cancer. A variety of transcription inhibitors can downregulate the expression of E-cadherin, including Snail, ZEBl, ZEB2 and so on. The zinc finger transcription factor Slug protein is belonged to the family of Snail zinc finger transcription factor,which can combine with E-boxes the promoter region of E-cadherin and ihibite the expression of it. The increased expression of Slug may lead to the occurrence of EMT, so it is very important to study the molecular mechanism of recurrence and metastasis in patients with non small cell lung cancer. Zinc finger E box binding protein 1 is an important member of the zinc finger transcription factor family which is a transcription factor that is essential for the development of the embryo. Studies at home and abroad have demonstrated that ZEB1 inhibits the expression of E-cadherin and promotes the occurrence of EMT directly or indirectly, which will increase the ability of multiple tumor invasion and metastasis. The expression of E-cadherin, ZEB1 and Slug in 136 lung cancer specimens and 30 cases of lung cancer were detected by immunohistochemistry SP. The purpose of the study was to explore the relationship between the three factors and the clinical pathological factors of non small cell lung cancer, and to provide evidence for the study of the molecular mechanism of the invasion and metastasis of non-small cell lung cancer.Objective To investigate the expression of Slug protein ? ZEB1 and E-cadherin in specimens of non-small-cell lung cancer(NSCLC) and adjacent normal tissues, analysis its correlation with ZEB1 or E-cadherin. In addition, the relationship between Slug?ZEB1?E-cadherin and clinical pathological characteristics, linical significance and prognostic value were studied.Methods In this study, 136 patients with non small cell lung cancer were collected from the First Affiliated Hospital of Zhengzhou University from January 2011 to April 2013. All patients were treated with radiotherapy and chemotherapy before operation. Among them, 102 were male and 34 were female, aged from 39 to 77 years old. The other 30 cases were taken as the control group, including 18 males and 12 females, aged from 40 to 75 years. In the specimens of lung cancer, 60 cases of them were squamous cell carcinoma, 76 cases of them were adenocarcinoma; 56 cases with lymph node metastasis, 80 cases without lymph node metastasis; 102 cases were in stage I ~ II, 34 cases were in stage III-IV. All lung cancer samples and the adjacent tissues were fixed with 10% formalin, paraffin embedded, by hematoxylin and eosin staining pathological diagnosed. Patients were treated with regular four cycles of chemotherapy, including gemcitabine+ oxaliplatin, docetaxel + nedaplatin, training melody match + nedaplatin, gemcitabine and nedaplatin, docetaxel + cisplatin, respectively; all of which were not given biological treatment and targeted therapy. Immunohistochemistry method was used to detect the expression of Slug, ZEB1 and E-cadherin in tissues. Statistical analysis of all data using SPSS15.0 statistical software.Results 1. Slug protein positive staining was located in the nucleus or cytoplasm, all dyed brown; ZEB1 protein positive staining was located in cytoplasm and nucleus; E-cadherin protein positive staining was located in cell membrane and cytoplasm. In non small cell lung cancer the expression rate of Slug, ZEB1 and E-cadherin were 67.65%(92/136), 54.41%(74/136) and 50.00%(68/136) respectively, while they were 13.4%(4/30), 23.3%(7/30) and 90.0%(27/30) in adjacent normal tissues, and the the expression of difference of the three kinds of protein were significant in non small cell lung cancer tissues and adjacent tissues(P < 0.05). 2. There is no correlation between the positive expression of E-cadherin, Slug and ZEB1 protein with sex, age and histological type in in the tissues of NSCLC(P >0.05); while they were related with cancer differentiation, TNM staging and lymph node metastasis(P value <0.05). 3. There was a positive correlation between the expression of Slug and ZEB1(rs=0.388, P=0.001); there was a negative correlation between the expression of Slug and E-cadherin(rs=-0.228, P=0.010); and the correlation between the expression of ZEB1 and E-cadherin is negative(rs=-0.267, P=0.021). 4. The progression free survival time of the patients with positive expression of Slug protein and negative expression were 11 months and 17 months. The difference in the PFS curves between the two groups was significant(?2=5.217,P=0.022). The progression free survival time of the patients with positive expression of ZEB1 protein and negative expression were 11 months and 16 months. The difference in the PFS curves between the two groups was significant(?2=6.996, P=0.008). The progression free survival time of the patients with positive expression of E-cadherin protein and negative expression were 16 months and 10 months. The difference in the PFS curves between the two groups was significant(?2=8.045,P=0.005).Conclusion 1. Reduced expression of E-cadherin and enhanced expression of Slug and ZEB1 indicated that NSCLC patients were more prone to lymph node metastasis and poor prognosis, suggesting that it could be used as an important indicator to judge the prognosis of NSCLC. 2. In NSCLC, the expression of Slug and ZEB1 was positively correlated. Slug and ZEB1 may inhibit the expression of E-cadherin through synergistic action, and then promote the occurrence of EMT. |
PDF Full Text Request