Expression Of Kiss-1, Mmp-9 And Timp-1 In Gastric Carcinoma And Its Significance

Infiltration and metastasis of a malignant tumor is a complicated process that involves many factors as invasion and adhesion of tumor cells, interaction between tumor cells and mesenchyma. KISS-1 is a recently found human metastasis suppressor gene. Its expression occurs in normal and non-metastatic tumor cell lines, whereas loss of KISS-1 expression occurs in metastatic tumor tissue. Researches indicates that KISS-1 can inhibit infiltration and metastasis of tumor by inducing adhesion of tumor cells to restrain its migratory potential and suppressing matrix metalloproteinases (MMPs) activity to lower the hydrolysis of extracellular matrix(ECM).MMPs are a family of zinc dependent enzymes that cleave various components of ECM as collagenases, gelatinases, stromelysins. MMP-9, one important member of the family, may become type IV Collagenase after being activated which can degrade and destroy surface collagen and gelatin and result in infiltration and metastasis of tumor cells through damaged basement membrane to surrounding tissue.Tissue inhibitor of matrix metalloproteinases(TIMPs) are the selective inhibitors of MMPs. Among all TIMPs, TIMP-1 has the strongest effect. The synergy of TIMP-1 and MMP-9 maintains the dynamic balance between injury and repair of ECM which plays an important role in inhibiting infiltration and metastasis of tumor. The morbidity and mortality of gastric carcinoma are all high. In china, the morbidity of gastric carcinoma takes the first in digestive tumors. 160,000 die from gastric cancer each year. The leading causes of the mortality are infiltration and metastasis of gastric cancer. So exploring the. mechanism of the invasion and metastasis of gastric carcinoma has become one of research hot spots.To this date, domestic and foreign documents have no reports on researches in expression and significance of KISS-1, MMP-9 and TIMP-1 in gastric carcinoma.In order to discuss the mechanisms of infiltration and metastasis of gastric carcinoma and search valid methods which can suppress the infiltration and metastasis of gastric carcinoma, this research adopts immunohistochemistry SP method to observe the expression of KISS-1, MMP-9 and TIMP-1 in 45 cases of gastric carcinoma tissues, 23 cases of adjacent non-atypical hyperplasia tissues and 21 cases of normal mucosa tissues. Detecting unitedly illuminates furtherly the mechanisms of infiltration and metastasis of gastric carcinoma and provides theory foundation for blocking infiltration and metastasis of gastric carcinoma.Methods1. Using the immunohistochemistry SP technology to detect the expression of KISS-1,MMP-9 and TIMP-1 in the 45 cases of gastric carcinoma, 23 cases of tumor-adjacent atypical hyperplasia tissues and 21 cases of normal mucosa of gastric carcinoma respectively.2. Statistical analysis: All the data were analyzed by SPSS 12.0 statistical package. The Chi-square was used in the comparison of positive rates; The relation of two variables were analyzed by the spearman level correlation analysis. The level of significant difference wasα=0.05.Results1. The positive expression rates of KISS-1 protein in normal mucosa of stomach , atypical hyperplasia tissues,and carcinoma tissues were 90.48%(19/12), 60.87% (14/23) and 35.56%(16/45) respectively;the positive expression rate of KISS-1 protein in the carcinoma tissues was compared with that in the propotional adjacent tissues and normal mucosa tissues from each other, there was statistical significance(P <0.05).2. The positive expression rates of MMP-9 protein in normal mucosa of stomach, atypical hyperplasia tissues, and carcinoma tissues were 9.52%(2/21), 34.78%(8/23) and 60.00%(27/45) respectively; the positive expression rate of MMP-9 protein in the carcinoma tissues was compared with that in the propotional adjacent tissues and normal mucosa tissues from each other, there was statistical significance(P <0.05).3. The positive expression rates of TIMP-1 protein in normal mucosa of stomach, atypical hyperplasia tissues and carcinoma tissues were 95.24%(20/21), 65.22%(15/23) and 40%(18/45) respectively, the positive expression rate of TIMP-1 protein in the carcinoma tissues was compared with that in the propotional adjacent tissues and normal mucosa tissues from each other, there was statistical significance(P <0.05).4. In the 22 cases of metastatic group, the positive rate of expression of KISS-1 protein in the tumor tissues was 18.18%(4/22); in the non-metastatic group, it was 52.17% (12/23). There was significant difference between the two groups (P<0.05).5. In the 22 cases of metastatic group, the positive rate of expression of MMP-9 protein in the tumor tissues was 77.27%(17/22); in the non-metastatic group, it was 43.48% (10/23). There was significant difference between the two groups (P<0.05).6. In the 22 cases of metastatic group, the positive rate of expression of TIMP-1 protein in the tumor tissues was 22.73%(5/22); in the non-metastatic group, it was 65.00% (13/23). There was significant difference between the two groups (P<0.05).7. In the tissues of gastric carcinoma, the positive rates of expression of KISS-1 protein on the low-muscle invaded, deep-muscle invaded and outer layer invaded were 57.14%(8/14), 46.67%(7/15) and 6.25%(1/16) respectively. The expression of KISS-1 in the carcinoma tissues with the outer layer invaded was evidently lower than that in the tissue with low-muscle invaded and deep-muscle invaded. There was significant difference among the groups(P<0.05). Thus the expression of KISS-1 in the carcinoma tissues with deep-muscle was compared with that with low-muscle, there was no significance (P>0.05).8. In the tissues of gastric carcinoma, the positive rates of expression of MMP-9 protein on the low-muscle invaded, deep-muscle invaded and outer layer invaded were 28.57%(4/14), 66.67%(10/15) and 81.25%(13/16) respectively. The expression of MMP-9 in the carcinoma tissues with the outer layer invaded was evidently higher than that in the tissue with low-muscle invaded and deep-muscle invaded. There was significant difference among the groups(P<0.05). Thus the expression of MMP-9 in the carcinoma tissues with deep-muscle was compared with that with outer layer, there was no significance (P>0.05).9. In the tissues of gastric carcinoma, the positive rates of expression of TIMP-1 protein on the low-muscle invaded, deep-muscle invaded and outer layer invaded were 64.29% (9/14),46.67% (7/15) and 12.50%(2/16) respectively. The expression of TIMP-1 in the carcinoma tissues with the outer layer invaded was evidently lower than that in the tissue with low-muscle invaded and deep-muscle invaded. There was significant difference among the groups(P<0.05). Thus the expression of TIMP-1 in the carcinoma tissues with deep-muscle was compared with that with low-muscle invaded, there was no significance (P>0.05).10. The relativity of the expression of KISS-1, MMP-9 and TIMP-1 in gastric carcinoma was analyzed statistically. Results showed that the expression of KISS-1 was negatively correlated with that of MMP-9 , positively correlated with that of TIMP-1. The later two were positively correlated(P<0.01).Conclusions1. The positive rates of the expression of KISS-1 protein in normal mucosa tissues, tumor-adjacent atypical hyperplasia tissues and gastric carcinoma tissues of stomach were low in turn. It indicated that KISS-1 participated in occurrence and development of gastric carcinoma. The positive rates of the expression of KISS-1 protein in gastric carcinoma tissues decreased gradually accompanied with the invasion depth, the expression of KISS-1 in gastric carcinoma tissues with lymphnode metastasis was lower than that in without lymphnode metastasis, It indicated that KISS-1 participated in infiltration and metastasis of gastric carcinoma.2. The positive rates of the expression of MMP-9 protein in normal mucosa tissues, tumor-adjacent atypical hyperplasia tissues and gastric carcinoma tissues of stomach were high in turn. It indicated that MMP-9 participated in occurrence and development of gastric carcinoma. The positive rates of the expression of MMP-9 protein in gastric carcinoma tissues increased gradually accompanied with the invasion depth, the expression of MMP-9 in gastric carcinoma tissues with lymphnode metastasis was higher than that in without lymphnode metastasis, It indicated that MMP-9 participated in infiltration and metastasis of gastric carcinoma.3. The positive rates of the expression of TIMP-1 protein in normal mucosa tissues, tumor-adjacent atypical hyperplasia tissues and gastric carcinoma tissues of stomach were low in turn. It indicated that TIMP-1 participated in occurrence and development of gastric carcinoma. The positive rates of the expression of TIMP-1 protein in gastric carcinoma tissues decreased gradually accompanied with the invasion depth, the expression of TIMP-1 in gastric carcinoma tissues with lymphnode metastasis was lower than that in without lymphnode metastasis, It indicated that TIMP-1 participated in infiltration and metastasis of gastric carcinoma.4. The relativity of the expression of KISS-1, MMP-9 and TIMP-1 protein was analyzed statistically. Results showed relative and they played a synergistic effect during the process of occurrence and development and infiltration, metastasis of gastric carcinoma.