Expression Of CD147,TGF-β1,MMP-2 And TIMP-2and Its Significance In Thyroid Carcinoma

Background and objective:Tumor is one of the most dangerous diseases that threat human’s health seriously,especially the malignant tumor.The most fundamental biological characteristics of tumor are invasion and metastasis,90% of patients died of tumor recurrence or metastasis.Tumor invasion and metastasis is a multi-step and complex process,which include adhesion,dissolution,transfer and secondary growth,etc.Tumor cells and intercellular substance can secrete some soluble molecule by autocrine and paracrine to accomplish immune escape,tumor metastasis and angiogenesis.These soluble molecule include TGF,MMPs and CD147,etc.The matrix metalloproteinase-2(MMP-2)is a type IV collagenase,which can degrade collagen of type IV and V,what else,they can degrade elastic fibers and promote the reshape of macromolecule in cytomembrane.It also play an important role in tumor invasion and metastasis.Tissue inhibitor of metalloproteinases(TIMP-2)is a natural inhibitor of MMP-2,the imbalance of TIMP-2 and MMP-2 promote the degrade of basilar membrane,and then accelerate tumor invasion and metastasis.CD147 is a transmembrane glycoprotein and a member of the immunoglobulin superfamily.It is highly expressed in various of malignant tumors,such as glioma,laryngeal squamous cell carcinoma,giant cell tumor of bone,melanoma,and its expression is closely related to tumor invasion and metastasis.In recently years,there are studies shows that not only up-regulation of CD147 can promote the secretion of MMPS,but also the increase of MMP-S can promote CD147,which develop an harmony balance and that’s one of the forms of positive feedback tumor stroma interaction,then promotes tumor invasion and metastasis.TGF-β1 is the most common type of transforming growth factor family,and it is closely related to tumor.At present,there is no report on the expression of protein MMP-2,CD147,TGF-β1,TIMP-2 and TGF-β1mRNA in thyroid carcinoma.In this research,we take immunohistochemistry and hybridization in situ to test the expression of protein MMP-2,CD147,TGF-β1,TIMP-2 and TGF-β1mRNA in four types of thyroid carcinoma and normal tissues(nodular goiter and normal tissues).Combine with the clinical pathology data,we can explore the impact of four types of thyroid carcinoma in tumor invasion and metastatic process.we hope we can find a new target for the treatment of thyroid carcinoma,and make new contribution for the clinical treatment of thyroid cancer.Methods:1.Archival paraffin blocks of 233 cases of thyroid tissue which are come from the first affiliated hospital of Zhengzhou University are analyzed by immunohistochemical staining and FISH(fluorescence in situ hybridization),including 173 cases of thyroid carcinoma tissue(84 papillary thyroid carcinoma,38 follicular thyroid carcinomas,40 medullary thyroid carcinoma,11 undifferentiated thyroid carcinoma),30 cases of nodular goiter tissue and 40 cases of normal thyroid tissue,which were detected to find out the expression of CD147,TGF-β1,MMP-2,TIMP-2 protein and TGF-β1mRNA.2.Statistical analysis : SPSS21.0 software was used for quantitative analysis.Using chi-square to compare two positive rate,Using spearman rank correlation to analyze two-variable correlation.Inspection level α=0.05.Results:1.In 173 cases of thyroid carcinoma tissue,the positive expression rate of protein CD147 is 71.10 percent(123/173),and in 30 cases of nodular goiter tissue,the positive expression rate of protein CD147 is 6.67 percent(2/30).In 30 cases of normal thyroid tissue,there are no positive expression.The expression of protein CD147 is significantly higher in thyroid carcinoma tissue than in non-carcinoma tissues,the difference is statistically significant(P<0.05).There was no significant difference between the expression of protein CD147 and the sex,age and tumor histologic type of thyroid cancer patients(P > 0.05).The positive expression rate of protein CD147 in greater or equal to 1 cm in diameter group is 66.15 percent(86/130),but in less than 1 cm in diameter group is 86.05 percent(37/43),the difference is statistically significant(P<0.05).The positive expression rate of protein CD147 in lymph node metastas positive patient group is 79.17 percent(57/72),and negative group is 65.35 percent(66/101),the difference is statistically significant(P<0.05).2.In this paper,the positive expression rate of protein TGF-β1in thyroid carcinoma tissue,nodular goiter tissue and normal thyroid tissue are 61.85 percent(107/173),20.00 percent(2/30),6.67 percent(2/30)respectively.The expression of protein TGF-β1 is significantly higher in thyroid carcinoma tissue than in non-carcinoma tissues,the difference isstatistically significant(P<0.05).There was no significant difference between the expression of protein TGF-β1and the sex,age and tumor histologic type of thyroid cancer patients(P > 0.05).The positive expression rate of protein TGF-β1 in greater or equal to 1 cm in diameter group and less than 1 cm in diameter group are 56.92 percent(74/130)and 76.74 percent(33/43)respectively,the difference is statistically significant(P<0.05).The positive expression rate of protein TGF-β1 in lymph node metastasis positive patient group and negative group are 76.39 percent(55/72)and 51.49 percent(52/101)respectively,the difference is statistically significant(P<0.05).3.In this paper,the positive expression rate of TGF-β1 mRNA in thyroid carcinoma tissue,nodular goiter tissue and normal thyroid tissue are 61.85 percent(97/173),10.00 percent(3/30),3.33 percent(1/30)respectively.The expression of TGF-β1 mRNA is significantly higher in thyroid carcinoma tissue than in non-carcinoma tissues,the difference is statistically significant(P<0.05).There was no significant difference between the expression of TGF-β1 mRNA and the sex,age and tumor histologic type of thyroid cancer patients(P > 0.05).The positive expression rate of TGF-β1 mRNA in greater or equal to 1 cm in diameter group and less than 1 cm in diameter group are 51.54 percent(67/130)and 69.77%(30/43)respectively,the difference is statistically significant(P<0.05).The positive expression rate of TGF-β1 mRNA in lymph node metastasis positive patient group and negative group are 65.28%(47/72)and 49.50 percent(50/101)respectively,the difference is statistically significant(P<0.05).4.In 173 cases of thyroid carcinoma tissue,the positive expression rate of protein MMP-2 is 60.00 percent(102/173).In 30 cases of nodular goiter tissue,the positive expression rate of MMP-2 protein is 13.3 percent(4/30).In 30 cases of normal thyroid tissue,the positive expression rate of MMP-2 is 6.67 percent(2/30).The expression of protein MMP-2 is significantly higher in thyroid carcinoma tissue than in non-carcinoma tissues,the difference is statistically significant(P<0.05).The positive expression rate of protein MMP-2 in papillary thyroid carcinoma,follicular thyroid carcinomas,medullary thyroid carcinoma,undifferentiated thyroid carcinoma are 70.24 percent(59/84),52.63 percent(20/38),42.50 percent(17/40),54.55 percent(6/11)respectively.The positive expression rate of protein MMP-2 in papillary thyroid carcinoma is the highest,the difference between medullary thyroid carcinoma and papillary thyroid carcinoma is statistically significant(P<0.05).There was no significant difference between the expression of protein MMP-2 and the sex,age of thyroid cancer patients(P > 0.05).The positive expression rate of protein MMP-2 in greater or equal to 1 cm in diameter group is 53.85 percent(70/130),but in less than 1 cm in diameter group is 74.42 percent(32/43),the difference is statistically significant(P<0.05).The positive expression rate of protein MMP-2 in lymph node metastasis positive patient group is 68.06 percent(49/72),and negative group is 52.48 percent(53/101),the difference is statistically significant(P<0.05).5.In this paper,the positive expression rate of protein TIMP-2 in thyroid carcinoma tissue,nodular goiter tissue and normal thyroid tissue are 60.69 percent percent(105/173)respectively,6.67 percent(2/30),3.33percent(1/30).The expression of protein TIMP-2 is significantly higher in thyroid carcinoma tissue than in non-carcinoma tissues.the difference is statistically significant(P<0.05).The positive expression rate of protein TIMP-2in papillary thyroid carcinoma,follicular thyroid carcinomas,medullary thyroid carcinoma,undifferentiated thyroid carcinoma are 47.62 percent(40/84),65.79 percent(25/38),75.00 percent(30/40),91 percent(10/11)respectively.The positive expression rate of protein TIMP-2 in anaplastic thyroid carcinoma is the highest,the difference between anaplastic thyroid carcinoma and papillary thyroid carcinoma is statistically significant(P <0.05).There was no significant difference between the expression of protein TIMP-2 and the sex,age of thyroid cancer patients(P > 0.05).The positive expression rate of protein TIMP-2 in greater or equal to 1 cm in diameter group is 57.69 percent(75/130),but in less than 1 cm in diameter group is 69.77 percent(30/43),the difference is statistically significant(P <0.05).The positive expression rate of protein TIMP-2 in lymph node metastasis positive patient group is 69.44%(50/72),and negative group is 54.46 percent(55/101),the difference is statistically significant(P<0.05).6.In 173 cases of thyroid carcinoma tissue,it had shown positive correlation among protein CD147 and protein MMP-2(r=0.453,P<0.05),protein CD147 and protein TIMP-2(r=0.296,P<0.05),protein CD147 and protein TGF-β1(r=0.733,P<0.05),protein MMP-2 and protein TIMP-2(r=0.171,P<0.05),protein MMP-2 and protein TGF-β1(r=0.409,P<0.05),protein TIMP-2 and protein TGF-β1(r=0.391,P<0.05),TGF-β1mRNA and protein TGF-β1(r=0.815,P<0.05).Conclusion:1.The expression rate of protein CD147,TGF-β1,MMP-2,TIMP-2 and TGF-β1mRNA in thyroid cancer is significantly higher than that in non-cancer tissues,suggesting that it may be involved in the occurrence of thyroid cancer.2.The positive expression rate of protein CD147,TGF-β1,MMP-2,TIMP-2 and TGF-β1mRNA increased with the increase of lymph node metastasis rate,suggesting that it may be related to lymph node metastasis of thyroid cancer.3.All the expression rate of protein CD147,TGF-β1,MMP-2,TIMP-2 and TGF-β1mRNA in thyroid cancer is high,and there is a positive correlation among them,suggesting that the four may play a synergistic role in the occurrence of thyroid cancer and lymph node metastasis process.