Expression Of INOS, COX—2, IL-8 And UPA In Gastric Cancer And Their Relationship With Tumor Angiogenesis

Objective To investigate the expression of VEGF, iNOS, COX-2, IL-8, uPA and PAI-1 in gastric cancer (GC) and their relationship with tumor angiogenesis and clinical pathological features. Methods Part 1: Immunohistochemical staining (S-P method) for VEGF, iNOS, COX-2, IL-8 protein and microvessel density (MVD) were performed in 67 cases of GC; Part2: uPA, PAI-1 mRNA and protein expression and MVD in 110 cases of GC were examined by using of tissue microarray and in situ hybridization immunohistochemical staining technique respectively. Results Part 1: 1. Of 67 cases of GC, MVD was negatively correlated with the 5 year survival rate. 2. Of 67 cases of GC, the high expression rates of VEGF, iNOS, COX-2, IL-8 protein were respectively 76.1%, 68.7%, 76.1% and 67.2%. The expression of VEGF, iNOS, IL-8 protein in well differentiated adenocarcinoma were significantly higher than those in poor differentiated adenocarcinoma (P<0.05). There was a statistical difference of the expression of COX-2 protein among well, moderate and poor differentiated adenocarcinoma(P<0.05). 3. MVD were significantly higher in VEGF, iNOS, COX-2, IL-8-high expression group in GC than in VEGF, iNOS, COX-2, IL-8-negative and low expression group in GC (P<0.05). 4. The high expression of VEGF, iNOS, COX-2, IL-8 protein positively correlated with the depth of invasion (P<0.001), the high expression of iNOS, IL-8 protein positively correlated with the clinical stage (P<0.05). 5. There was a significant positive correlationship between the expressions of iNOS, COX-2 and VEGF protein. 6. Multivariate Cox regression analysis indicated that MVD and lymph node metastasis were independentprognostic factors that affected survival in GC. Part2: 1. Of 110 cases of GC, the expression rates of uPA, PAI-lmRNA and protein were respectively 56.4% and 67.3%, 55.5% and 66.4%, there was a statistical difference of the expression of uPA and PAI-1 among different differentiated adenocarcinoma (P <0.05). 2. MVD were significantly higher in uPA-positive expression group than in uPA-negative expression group in GC (P<0.05). 3. The expression of uPAmRNA and protein was significantly correlated with the clinical stage of GC (P<0.05). The expression of PAI-lmRNA and protein negatively correlated with the clinical stage and lymph node metastasis while the difference was not significant (P=0.635,0.374). 4. There was a negative correlationship between the expression of uPA, PAI-lmRNA (protein) in GC while the difference was not significant. Conclusion 1. MVD may be one of the important predictors for the malignant and survival rates of GC, it is helpful for predicting the angiogenesis and prognosis of GC to detect the MVD; 2. VEGF, iNOS, COX-2, IL-8, uPA may be factors that contribute to GC angiogenesis, to hold back the secretion and passways of the above factors may be a new treatment for GC. 3. PAI-1 may be an inhibitor factor in the growth, invasion and metastasis of GC. 4. iNOS, COX-2 may promote angiogenesis through the way of VEGF. 5. Tissue microarrary technology has important practical significance and broad application prospect in pathology.