Expression Of TFPI-2 And SNCG In Esophageal Cancer And The Correlation Between TFPI-2 And SNCG And Esophageal Cancer Local Invision, Lymph Node Metastasis And The Apoptosis

Background and purposeEsophageal cancer is one of the most common malignant neoplasms in the dligestive system.It was the fourth in the death rate of malignant tumor in our country.Invasion and metastasis is the important reason for death of Esophageal carcinoma.Invasion and metastasis of Esophageal carcinoma is complexed course which is involved in multiple gene throng multiple factor and steps.Invasion and metastasis of malignant tumor is correlated with hydrolysis of extracellular matrix closely. The balance of prolease and proteinase inhibitors influences bionomics of tumor directly. Extracellular Matrix and basilar membrane are barrier to prevent invasion and metastasis of malignant tumor. Raising prolease or reducing proteinase inhibitors result in hydrolysis and failure of extracellular and basilar membrane, which promote invasion and matastasis of esophageal carcinoma.Tissue factor pathway inhibitor-2 (TFPI-2) previously designated as placental protein5, a member of the Kunitz-type serine proteinase inhibitor family, is a structural homologue of TFPI. TFPI-2 inhibits a wide variety of serine proteinases including plasmin, trypsin, matrix metalloproteinases.Matrix metalloproteinases is a important role in fibrinolysis, atherosclerosis, wound healing, invasion and matastasis of tumor, angiogenesis and extracellular matrix's remolding. TFPI-2 controls invasion and matastasis of many kinds of malignant tumor cell through keeping integrity of extracellular matrix, regulating tumor cell apoptosis and hemopexis, resisting angiogenesis. The study suggest TFPI-2 obviously inhibits activity and function of matrix metalloproteinases in tumor, thus prohibit invasion and matastasis of malignant tumor.y-synuclein (SNCG) is a member of neuronal protein synuclein family, at commom state, it is mainly distributed in nervous system, which has tissue specificity evidently.γ-synuclein was previously found in cDNA library of breast carcinoma, which was known as breast cancer specific gene (BCSG1). At present, it was widely studied in breast cancer as tumor marker. Resently, abnormal expression of y-synuclein was found in digestive system neoplasms including hepatic carcinoma, gastire carcinoma, pancreatic cancer.γ-synuclein can enhance ability of invasion and metastasis of tumor cell and resisting anti-tumor drug, which make it become new tumor maker and therapeutical target.To detect the expression of TFPI-2 and SNCG in the tumor tissues, the tissues of atypical hyperplasia of tumor-adjacent and normal tissues and their roles in invasion and metastasis of esophageal cancer as well as relationship with MMP-9, apoptosis, which provide new reference for forecasting the carcinogenesis, treatment and judge prognosis of esophageal cancer.Materials and Methods(1) 82 esophageal carcinoma tissues,20 the tissues of atypical hyperplasia of tumor-adjacent and 54 normal tissues were collected in An Yang cancer hospital. All the tissues were fixed in 10% neutral formalin and embedded in paraffin.(2) The expression of TFPI-2,SNCG and MMP-9 was detected by immunohistochemistry S-P methods and the apoptosis of esophageal cancer histiocyte was detected using TUNEL in 82 esophageal carcinoma tissues,20 the tissues of atypical hyperplasia of tumor-adjacent and 54 normal tissues.(3) All of the experimental data was performed with statistical package spss 11.0 software.The compassion of positive rates applies the Chi-square,pearson stage relate analysis.Association between parameters was assess by t-test, statistically significant level was considered as "a=0.05"Result(1)The result of TFPI-2 detection:The positive expression of TFPI-2 was located in cytoplasm and membrane. The positive rates of expression of TFPI-2 protein in the tumor tissues, the tissues of atypical hyperplasia of tumor adjacent and normal tissues were 30.487%,60.000% and 87.037%, respectively, there was a significant difference among the three groups(p<0.05). The positive rates of expression of TFPI-2 of well-differentiation groups, without involucre invasion group, without lymph node metastasis group andⅠ-ⅡTNM stage group were 64.000%,91.304%,85.714%, 84.000%, respectively, which were higher than moderate-poor differentiation groups 26.316%, involucre invasion group 61.017%, lymph node metastasis group 52.500%, III-IV TNM stage group 48.875%. (p<0.05). However, The positive rates of expression of TFPI-2 isn't related with age gender, tumor location diameter, pathologic histotype. (p<0.05).(2) The result of SNCG detection:The positive expression of SNCG was located in cytoplasm and membrane. The positive rates of expression of SNCG protein in the tumor tissues, the tissues of atypical hyperplasia of tumor adjacent and normal tissues were 63.414%,30.000% and 3.703%, respectively, there was a significant difference among the three groups (p<0.05). The positive rates of expression of SNCG of well-differentiation groups,without involucre invasion group, without lymph node metastasis group andⅠ-ⅡTNM stage group were 44.000%,30.435%,47.619%, 48.000%, respectively, which were lower than moderate-poor differentiation group, 71.930%, involucre invasion group 76.271%, lymph node metastasis group 80.000%, III-IV TNM stage group 87.500%.(p<0.05). However, The positive rates of expression of SNCG isn't related with age gender, tumor location diameter, pathologic histotype. (p<0.05)(3)The result of MMP-9 detection:The positive expression of MMP-9 was located in cytoplasm and membrane. The positive rates of expression of MMP-9 protein in the tumor tissues, the tissues of atypical hyperplasia of tumor adjacent and normal tissues were 71.951%,40.000% and 11.111%, respectively, there was a significant difference among the three groups (p<0.05). The positive rates of expression of MMP-9 of well-differentiation groups,without involucre invasion group, without lymph node metastasis group andⅠ-ⅡTNM stage group were 56.000%,43.478%,54.762%, 60.000%, respectively, which were lower than moderate-poor differentiation group, 78.947%, involucre invasion group 83.051%, lymph node metastasis group 90.000%, III-IV TNM stage group 90.625%.(p<0.05). However, The positive rates of expression of SNCG isn't related with age gender, tumor location diameter, pathologic histotype. (p<0.05)(4)The relationship of TFPI-2 and MMP-9 of esophageal cancer tissue:The positive expression of TFPI-2 and MMP-9 of 82 esophageal cancer tissue was 4 cases.The simultaneously negative was 2 cases. Pearson correlation analysis found that TFPI-2 had a negitive correlation with MMP-9(r=-0.636,p=0.000)(5) The relationship of SNCG and MMP-9 of esophageal cancer tissue:The positive expression of SNCG and MMP-9 of 82 esophageal cancer tissue was 45 cases.The simultaneously negative was 16 cases.Pearson correlation analysis found that SNCG had a positive correlation with MMP-9(r=0.393,p=0.000)(6) The relationship of TFPI-2 and SNCG of esophageal cancer tissue:The positive expression of TFPI-2 and SNCG of 82 esophageal cancer tissue was 12 cases.The simultaneously negative was 17 cases.Pearson correlation analysis found that TFPI-2 had no correlation with SNCG(r=-0.207,p=0.055)(7)The correlation between TFPI-2, SNCG and apoptosis:Apoptosis index of the positive of expression of TFPI-2 of esophageal cancer tissue (8.125±2.139) was higher than that of the negative expression (4.861±2.584),the difference between them was significant (p<0.05); Apoptosis index of the positive of expression of SNCG of esophageal cancer tissue (4.423±2.689) was lower than that of the negative expression (7.100±2.918),the difference between them was significant (p<0.05)Concolusion(1) The positive expression rate of TFPI-2 of esophageal cancer tissue was obviously lower than that of nomal esophageal tissue and tumor-adjacent.The low positive expression rate of TFPI-2 related with the differentiation of carcinoma, lymph node metastasis status,depth of tumor infiltration and the TNM staging,but not with age,gender,tumor lacation diameter and pathologic histotype.TFPI-2 is tumor suppressor,which participated carcinogenesis and progress of esophageal cancer.(2) The positive expression rate of SNCG of esophageal cancer tissue was obviously higher than that of nomal esophageal tissue and tumor-adjacent.The high positive expression rate of SNCG related with the differentiation of carcinoma, lymph node metastasis status, depth of tumor infiltration and the TNM staging, but not with age, gender, tumor lacation diameter and pathologic histotype.SNCG is oncogene,which participated carcinogenesis and progress of esophageal cancer.(3) The positive expression rate of MMP-9 of esophageal cancer tissue was obviously higher than that of nomal esophageal tissue and tumor-adjacent.The high positive expression rate of SNCG related with the differentiation of carcinoma, lymph node metastasis status,depth of tumor infiltration and the TNM staging,but not with age,gender,tumor lacation diameter and pathologic histotype.MMP-9 participated carcinogenesis and progress of esophageal cancer(4) TFPI-2 and MMP-9 was negatively correlated.The study suggest TFPI-2 inhibited invasion and metastasis of esophageal cancer through suppressing MMP-9, reducing destroy of ECM and keeping integrity of ECM and basilemma.(5) SNCG and MMP-9 was positively correlated,which suggest that they togetherly promoted invasion and metastasis of esophageal cancer.(6) The correlation of TFPI-2, SNCG and apoptotic index suggests TFPI-2 induced esophageal cancer cell apoptosis and inhibited growth and metastasis of tumor. SNCG promoted tumor cell multiplication,which result in invasion and metastasis of esophageal cancer through suppresing tumor cell apoptosis.(7) TFPI-2 and SNCG could to be a new tumor maker and the new target of gene therapy and offer the new reference for judge prognosis.