Expression And Clinical Significance Of Shh,Gli-1 And MMP-2 In Gastric Cancer

Gastric cancer is one of the digestive malignant tumors with high incidence rate in China and around the world,most of the patient aren't aware it easily due to insidious onset and nonspecific characteristics,majority of them have developed into middle even late when they found,and there are quite differences in terms of treatment,treatment effect and prognosis.The pathogenesis,diagnosis and treatment of gastric cancer have became a hot research field of digestive malignant tumors in current world.At present,some domestic and foreign researches about gastric cancer have showed that abnormal expression of Hedgehog(Hh)signaling pathway is highly related to gastric cancer's occurrence and development.Matrix metalloproteinase-2(MMP-2)is a member of matrix metalloproteinases family,plays a important role in malignant tumor infiltrating adjacent tissue and metastasis.The expression of Shh(Sonic Hedgehog),Gli-1(Glioma-associated hemolog-1)and MMP-2 proteins was examined by immunohistochemistry in the gastric cancer tissues and gastric polyp and the normal gastric mucosa tissues,analyze the correlation among Shh,Gli-1 and MMP-2,achieve the following objectives: 1.Identifying the abnormal expression of Hh signaling pathway do exist,figure out if any relation rest in the expression of MMP-2 and Hh signaling pathway's abnormal expression.2.Provide a new objective index of prognosis evaluation and brand new target of target therapy for clinical diagnosis and treatment.ObjectiveTo investigate the expression and clinical significance of Shh,Gli-1 and MMP-2 in gastric cancer tissue,analyze the relation between Shh,Gli-1,MMP-2 and clinicopathological characteristics of gastric cancer.Figure out the relation among the expression of MMP-2 and Hh signaling pathway's abnormal expression.Explore the possible effective mechanism of Shh,Gli-1 and MMP-2 within gastric cancer's occurrence,development and metastasis.To provide various objective indicators of prognosis evaluation and separate target of target therapy for clinical diagnosis and treatment.MethodsThe expression of Shh,Gli-1 and MMP-2 proteins were examined by immunohistochemistry in the human gastric cancer tissues and the human gastric polyp and the normal mucosa tissues of 40 cases,respectively gather the expression rate of Shh,Gli-1 and MMP-2 proteins,analyze the separated pathological type by gastric cancer's clinicopathological characteristics.Investigate the correlation of Shh,Gli-1 and MMP-2.Discuss the clinical significance and relation of each indicators,acquaint the function of Shh,Gli-1 and MMP-2 in the procedure of gastric cancer's occurrence,development and metastasis.Results1 The expression of Shh in gastric cancer tissues and the relation with clinicopathological characteristicsShh showed high level positive expression in gastric cancer tissues,the expression rate was 62.5%,low level positive expression in gastric polyp tissues and normal gastric mucosa tissues,the expression rates were 27.5% and 22.5% respectively,there were differed significantly(P<0.05).The expression level of Shh was not correlated with sex,age and histological type(P>0.05),the difference without statistical significance.The expression level of Shh was highly correlated with the degree of infringement,lymph node metastasis and pTNM stage(P<0.05),the difference has statistical significance.The expression rate of T3~T4 group was significantly higher than T1~T2 group,the expression rate of lymph node metastasis group was significantly higher than the non lymph node metastasis group(P<0.05),the difference was statistical significance.2 The expression of Gli-1 in gastric cancer tissues and the relation with clinicopathological characteristicsGli-1 indicated high level positive expression in gastric cancer tissues,the expression rate was 67.5%,the expression rate in gastric polyp tissues was higher than that in normal gastric mucosa tissues,the expression rate of gastric polyps was 37.5%,and the expression rate of normal gastric mucosa was 17.5%,there were differed significantly(P<0.05).The expression level of Gli-1 was not correlated with sex,age and histological type(P>0.05),the difference without statistical significance.The expression level of Shh was also relevant to the degree of infringment,lymph node metastasis and pTNM stage(P<0.05),the difference has statistical significance.The expression rate of T3~T4 group was significantly higher than T1~T2 group,the expression rate of lymph node metastasis group was significantly higher than the non lymph node metastasis group(P<0.05),the difference was statistical significance.3 The expression of MMP-2 in gastric cancer tissues and the relation with clinicopathological characteristicsMMP-2 revealed high level positive expression in gastric cancer tissues,the expression rate was 72.5%,the expression rate in gastric polyp tissues was higher than that in normal gastric mucosa tissues,32.5% and 12.5% respectively and statistically significant(P<0.05).The expression level of MMP-2 was not correlated with sex,age and histological type(P>0.05),the difference without statistical significance.The expression level of MMP-2 was closely relevant to the degree of infringement,lymph node metastasis and pTNM stage(P<0.05),the difference has statistical significance.The expression rate of T3~T4 group was obviously higher than T1~T2 group,the expression rate of lymph node metastasis group was significantly higher than the non lymph node metastasis group(P<0.05),the difference gained statistical significance.4 Relationship among the expression of Shh,Gli-1 and MMP-2 in gastric cancerSpearman rank correlation analysis showed that there was a positive correlation between the expression of Shh and Gli-1,r=0.521,P<0.05.The expression of Shh and Gli-1 indicated positive correlation,r=0.521,P<0.05.The expression of Shh and MMP-2 showed positive correlation,r=0.533,P<0.05.The expression of Gli-1 and MMP-2 presented positive correlation,r=0.531,P<0.05.Conclusion1 The expression of Shh and Gli-1Shh and Gli-1 are upstream factors of Hh signaling pathway.This experiment showed the high level expression of the factors above in gastric cancer tissue,but the expression levels were lower in gastric polyps and gastric mucosa,and the expression levels of these factors were closely relevant to positively to the degree of infringement,lymph node metastasis and pTNM stage.It is proved that there is a abnormal expression of Hh signaling pathway in gastric cancer tissues,and Hh signaling pathway was involved in the occurrence,development,invasion and metastasis of gastric cancer.The abnormal expression of Hh signaling pathway is one of the reasons for the occurrence of gastric cancer and promotes the progression,invasion and metastasis of gastric cancer.2 The expression of MMP-2MMP-2 is a member of matrix metalloproteinases family,with the biological activity of degrading extracellular matrix,it showed high level expression in gastric cancer tissues,and the expression was lower in gastric polyps and normal gastric mucosa,its expression level was related with tumor invasion depth,lymph node metastasis and pTNM stage,which can we speculated that MMP-2 was crucial in the process of invasion and metastasis of gastric carcinoma.3 Relationship among the expression of Shh,Gli-1 and MMP-2 in gastric cancerBy Spearman correlation analysis can be found,among the expression of Shh,Gli-1 and MMP-2 have a positive correlation,while Shh and Gli-1 are upstream factors of the Hh pathway,it can be speculated that Hh signaling pathway through a unclear mechanism of upregulating of MMP-2 expression level,so as to promote the invasion and metastasis of gastric cancer.