Integrin αvβ6 and matrix metalloproteinase 9 correlate with survival in gastric cancer

AIM: To investigate the expression of integrin alpha v beta 6 and matrix metalloproteinase 9 (MMP-9), their association with prognostic factors and to assess their predictive role in gastric cancer patients. METHODS: Immunohistochemistry was used to determine the expressions of integrin alpha v beta 6 and MMP-9 in 126 specimens from patients with primary gastric carcinoma. Associations between immunohistochemical staining and various clinic pathologic variables of tissue specimens were evaluated by the. 2 test and Fisher's exact test. Expression correlation of alpha v beta 6 and MMP-9 was assessed using bivariate correlation analysis. The patients were followed-up every 3 mo in the first two years and at least every 6 mo afterwards, with a median follow-up of 56 mo (ranging from 2 mo to 94 mo). Four different combinations of alpha v beta 6 and MMP-9 levels (that is, both markers positive, both markers negative, alpha v beta 6 positive with MMP-9 negative, and alpha v beta 6 negative with MMP-9 positive) were evaluated for their relative effect on survival. The difference in survival curves was evaluated with a log-rank test. Survival analysis was conducted using the Kaplan-Meier survival and Cox proportional hazards model analysis. RESULTS: The expressions of integrin alpha v beta 6 and MMP-9 were investigated in 126 cases, among which 34.92% were positive for alpha v beta 6 expression, and 42.06% for MMP-9 expression. The expression of alpha v beta 6 was associated with Lauren type, differentiation, N stage, and TNM stage (the P values were 0.006, 0.038, 0.016, and 0.002, respectively). While MMP-9 expression was associated with differentiation, T stage, N stage, and TNM stage (the P values were 0.039, 0.014, 0.033, and 0.008, respectively). The positive correlation between alpha v beta 6 and MMP-9 in gastric cancer was confirmed by a correlation analysis. The Kaplan-Meier survival analysis showed that patients with expression of alpha v beta 6 or MMP-9 alone died earlier than those with negative expression and that patients who were both alpha v beta 6 and MMP-9 positive had a shorter overall survival than those with the opposite pattern (both alpha v beta 6 and MMP-9 negative) (P = 0.000). A Cox model indicated that positive expression of alpha v beta 6 and MMP-9, diffuse Lauren type, as well as a senior grade of N stage, M stage, and TNM stage were predictors of a poor prognosis in univariate analysis. Only alpha v beta 6 and MMP-9 retained their significance when adjustments were made for other known prognostic factors in multivariate analysis (RR = 2.632, P = 0.003 and RR = 1.813, P = 0.007). CONCLUSION: The expression of alpha v beta 6 and MMP-9 are closely correlated, and the combinational pattern of alpha v beta 6 and MMP-9 can serve as a more effective prognostic index for gastric cancer patients.