Expression Of Macrophage Inhibitory Cytokine-1 (MIC-1) And Urokinase-type Plasminogen Activator(uPA) In Gastric Cancer And Its Significance

Objective: Macrophage inhibitory cytokine-1(MIC-1 )is a new member of the TGF-? superfamily. Recent studies have shown that in many pathologic states, such as acute injury, flame and tumorigenesis, the protein expression and serum level of MIC-1 will raise up remarkably, which suggests MIC-1 take an important role in many tumors'development or progression. Urokinase-type plasminogen activator(uPA) is a kind of serine proteolytic enzyme.It is reported that the uPA system has been implicated in the progression, metastasis, and angiogenesis of numerous malignant solid tumors. Reports in western literature indicate that MIC-1 can enhance the invasion ability of gastric cancer cells by up-regulating their uPA system. In this study, we detected the protein expression of MIC-1and uPA in normal gastric mucosa,gastritic mucosa and gastric carcinoma, analyzed its correlation with survival rate ,in order to reveal the role of the two markers in the carcinogenesis,development and prognosis of gastric cancer(GC).Methods:1 Randomly choosing 30 fresh GC specimens and 30 fresh normal gastric mucosa,46 GC paraffin sections with more than 3 years'followed-up and 12 cases gastritic mucosa confirmed through biopsy by gastroscope.2 S-P immunohistochemical staining was used to investigate the MIC-1 and uPA expression.3 SPSS13.0 software package was used to analyze the correlation between the expression of the two markers and the clinical parameters as well as the prognosis of GC patients. A statistically significant difference was indicated by a P<0.05.Results:1 The expression and clinical significance of MIC-1 in normal gastric mucosa,gastritic mucosa and gastric carcinoma.1.1 In gastric carcinoma the expression of MIC-1 was remarkably increased68.42%, compared with normal gastric mucosa specimens6.67%and gastritic mucosa25.00%(P<0.05). The expression was no difference between normal mucosa specimens and gastritic mucosa(P>0.05).1.2 In gastric carcinoma,the expression of MIC-1 were positive correlated with depth of invasion,lymph-node metastasis and TNM stage (P<0.01), but not with age, sex, tumor size and location, gross morphology and pathology histological grade (P>0.05).1.3 The 1- year and 3-year overall survival rate in the positive MIC-1 group were 71.88% and 12.50% , while 92.86%,and 78.57% in the negative group(P<0.01). These data indicated that MIC-1 was negative correlated with the prognosis of GC. 2 The expression and clinical significance of uPA in normal gastric mucosa,gastritic mucosa and gastric carcinoma.2.1 In gastric carcinoma the expression of uPA was remarkably increased67.11%, compared with normal gastric mucosa specimens10.11%and gastritic mucosa25.00%(P<0.05). The expression was no difference between normal mucosa specimens and gastritic mucosa(P>0.05).2.2 In gastric carcinoma,the expression of uPA were positive correlated with depth of invasion,lymph-node metastasis and TNM stage (P<0.01), but not with age, sex, tumor size and location, gross morphology and pathology histological grade (P>0.05).2.3 The 1- year and 3-year overall survival rate in the positive uPA group were 70.00% and 16.67% , while 93.75%,and 62.50% in the negative group(P<0.01). These data indicated that uPA was negative correlated with the prognosis of GC.3 Coexpression of MIC-1 and uPA were 43 cases in 76(56.58%)while 16 cases were completely negative for MIC-1 and uPA(21.05%)which indicated an association between MIC-1 and uPA in the carcinogenesis and development of GC (P<0.01).4 The1- and3-year overall survival rate in the coexpression group of MIC-1 and uPA were lower than uPA positive group or MIC-1 positive group (P<0.05).Conclusions: 1 MIC-1 and uPA may contribute to the occurring and progression of GC . In gastric carcinoma the expression of MIC-1 and uPA was remarkably increased compared with normal gastric mucosa and gastritic mucosa .MIC-1 and uPA were positively correlated with depth of invasion,lymph-node metastasis and TNM stage, but not correlated with age, sex, tumor size and location, gross morphology, pathology histological grade .2 The expression of MIC-1 and uPA were positively correlated in gastric carcinoma.3 The expression level of both MIC-1 and uPA were negatively correlated with gastric carcinoma prognosis,and combining the two markers would be more valuable than either in prognosis prediction.