| Background and objectiveIn the endocrine system and head and neck malignant tumors,the incidence of thyroid cancer ranks first,and in recent years the incidence rate showed an obvious upward trend,the most obvious growth is papillary carcinoma and tiny papillary carcinoma.Studies have suggested that the trend of growth may be related to over-diagnosis and the popularity of health examination,but also there are studies shown that early thyroid cancer have a better prognosis,and for distant metastasis and larger invasive thyroid cancer,the prognosis is very poor,according to reports,body environment factors,neck radiation,environment change and other factors can cause the incidence of thyroid cancer increased.Because the treatment of advanced thyroid cancer is very limited,it is necessary to study the potential mechanism which leading to thyroid cancer progression,so that it can provide new basis and ideas for the diagnosis and treatment of thyroid cancer.EMT(epithelial-mesenchymal transition)in cancer research is more concerned in recent years,The study found that it can occur in the embryonic development process,and it can also occur under the action of certain pathological factors,and it can play a role in organ fibrosis and tumor invasion and metastasis.Epithelial cells have a significant functional structural differences on the base surface,free surface and the side,which means epithelial cells have polarity,such as the junctions betweenthe side,such special structure can limit the abnormal migration of epithelial cells and can also play a coordinating function.After EMT,epithelial cells appear part of the characteristics of interstitial cells,these transformed cells lost polarity and cell connections,etc.obtain the ability to migrate.At the same time the two most important molecular markers which verify the EMT process are E-cadherin and Vimentin,the change of their expression can also be detected,it means the expression of E-cadherin was down-regulated and the expression of Vimentin was up-regulated.Many epithelial-derived tumors occur EMT in the early stages of invasion and metastasis,This process involves many transcription factors,which regulate gene expression.The process cause malignant tumor metastasis.Different genetic changes lead to different biological changes.Therefore,it is feasible to explore the relevant transcription factors involved in regulating EMT.Stat5(signal transducer and activator of transcription 5)is a member of the family of signal transduction and transcriptional activators.The stimulation of many cytokines,growth factor can cause Stat5 activation.Stat5 is mostly located in the cytoplasm before activation,it can be transposed into the nucleus after it is activated,then it can participate in the regulation of a series of downstream target gene's expression.The overexpression and abnormal activation of Stat5 protein can affect the formation and evolution of tumor,such as prostate cancer,breast cancer,leukemia,head and neck squamous cell carcinoma and lung cancer and other human malignancies.The abnormal expression of stat5 has been found in these malignacy diseases.But the study of Stat5's expression in thyroid cancer and related research are quite little both at home and abroad.At present,the expression of Stat5 and EMT-related molecular markers(E-cadherin,Vimentin)and the study of the interaction between them has not been reported in thyroid cancer,In this study,the expression of Stat5 and phosphorylated Stat5(P-Stat5)and E-cadherin and Vimentin in 126 thyroid carcinoma tissues were detected by immunohistochemistry,combined with clinical parameters for statistical analysis,inorder to explore their role in the development and evolution of thyroid cancer and the relationship between them,the whole study is looking forward to provide new ideas and theoretical basis for the diagnosis and effective treatment ofthyroid cancer.Methods1.Immunohistochemistry using streptavidin-peroxidase(Streptavidin-Peroxidase,SP)method,detected paraffin specimens of thyroid surgery archived by the Department of Pathology during 2011-2015,the First Affiliated Hospital of Zhengzhou University,then attached the specimen through 4?m continuous slicing to the adhesive slide.Immunohistochemistry was performed after 2 hours of oven baking at 60 ?,the dyeing process is strictly followed by instructions,using DAB color.2.The statistical processing of the obtained data were analyzed by SPSS 21.0statistical software.the positive expression rate comparison of Stat5 ? P-Stat5 ?E-cadherin and vimentin in the thyroid cancer and nodular goiter is Qualitative information,using ?2test and continuity correction.The correlation analysis of the expression of four proteins in thyroid carcinoma was analyzed by multiple groups of categorical variables,then got Pearson's R value.The test level ? = 0.05,P <0.05 indicates the difference was statistically significant.Results1.The positive expression of Stat5,P-Stat5 and Vimentin in thyroid carcinoma was 85.71%(108/126),54.76%(69/126),77.78%(98/126),which was significantly higher than that in nodular goiter 26.09%(6/23),13.04%(3/23),8.70%(2/23),The difference between the two groups was statistically significant(?2=38.477,?2=13.556,?2=38.983,P<0.05),the positive expression of E-cadherin in thyroid carcinoma was25.40%(32/126),significantly lower than 86.96%(20/23)in nodular goiter,the difference was statistically significant(?2=29.789,P<0.05).In the four histological categories of thyroid cancer,the positive expression of P-Stat5 and Vimentin in papillary carcinoma was higher than that in follicular carcinoma,medullary carcinoma and undifferentiated carcinoma tissues,the difference was statistically significant(P<0.05),the expression of E-cadherin in papillary carcinoma was lowerthan that of the other three kinds of cancer tissue,the difference was statistically significant(P<0.05).2.Combined with the relevant clinical pathological parameters,the statistics show that The expression of Stat5,P-Stat5,E-cadherin and Vimentin was associated with lymph node metastasis in thyroid carcinoma,but not with the age,sex and tumor diameter of thyroid cancer patients,the positive rates of Stat5,P-Stat5,E-cadherin and Vimentin were 88.10%(37/42),69.05%(29/42),14.29%(6/42),88.10%(37/42)in cases with lymph node metastasis was detected,the positive rates of the patients without lymph node metastasis were 84.52%(71/84),47.62%(40/84),72.62%(61/84)and 30.95%(26/84),the expression of P-Stat5,E-cadherin and Vimentin was statistically significant(?2=9.678,?2=4.105,?2=3.880,P<0.05),Stat5 expression in lymph node metastasis group was slightly higher than that in non-lymphatic metastasis group,but the difference was not statistically significant(?2=0.292,P>0.05).3.Through the association analysis,the results show there was a negative correlation between Stat5 and E-cadherin expression in thyroid carcinoma(r=-0.335),E-cadherin and Vimentin were negatively correlated(r=-0.609),Stat5 and Vimentin were positively correlated(r=0.218),the expression of Stat5 was positively correlated with that of P-Stat5(r=0.176).Conclusions1.The expression of Stat5,P-Stat5 and Vimentin was elevated and E-cadherin was down-regulated in thyroid carcinoma,suggesting that Stat5 may be involved in the development of thyroid cancer and the presence of epithelial-mesenchymal transition in thyroid carcinoma.2.P-Stat5,E-cadherin and Vimentin may be related to lymph node metastasis and pathological type,suggesting that they are involved in the development of thyroid cancer.3.Stat5 and P-Stat5 were positively correlated with the expression of Vimentin and negatively correlated with the expression of E-cadherin,and the expression ofE-cadherin and Vimentin was negatively correlated,it is suggests that Stat5 and its phosphorylated forms may be involved in the regulation of E-cadherin and Vimentin expression,thus induce epithelial-mesenchymal transition and affect the occurrence and evolution of thyroid carcinoma. |
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