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

AIM: To investigate the expression of integrin αvβ6 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 αvβ6 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 χ2 test and Fisher's exact test. Expression correlation of αvβ6 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 αvβ6 and MMP-9 levels(that is, both markers positive, both markers negative, αvβ6 positive with MMP-9 negative, and αvβ6 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 αvβ6 and MMP-9 were investigated in 126 cases, among which 34.92% were positive for αvβ6 expression, and 42.06% for MMP-9 expression. The expression of αvβ6 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 αvβ6 and MMP-9 in gastric cancer was confirmed by a correlation analysis. The Kaplan-Meier survival analysis showed that patients with expression of αvβ6 or MMP-9 alone died earlier than those with negative expression and that patients who were both αvβ6 and MMP-9 positive had a shorter overall survival than those with the opposite pattern(both αvβ6 and MMP-9 negative)(P = 0.000). A Cox model indicated that positive expression of αvβ6 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 αvβ6 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 αvβ6 and MMP-9 are closely correlated, and the combinational pattern of αvβ6 and MMP-9 can serve as a more effective prognostic index for gastric cancer patients.

Endocan-expressing microvessel density as a prognostic factor for survival in human gastric cancer

AIM: To investigate the expression of endocan in tumour vessels and the relationships between endocan and the expression of vascular endothelial growth factor(VEGF) and prognosis in gastric cancer.METHODS: This study included 142 patients with confirmed gastric cancer in a single cancer centre between 2008 and 2009. Clinicopathologic features were determined, and an immunohistochemical analysis of endocan-expressing microvessel density(MVD)(endocan-MVD), VEGF and vascular endothelial growth factor receptor 2(VEGFR2) was performed. Potential relationships between endocan-MVD and clinicopathological variables were assessed using a Student's t-test or an analysis of variance test. Spearman's rank correlation was applied to evaluate the relationship between endocan-MVD and the expression of VEGF/VEGFR2. long-term survival of these patients was analysed using univariate and multivariate analyses.RESULTS: Positive staining of endocan was observed in most of the gastric cancer tissues(108/142) and in fewer of the normal gastric tissues. Endocan-MVD was not associated with gender or histological type(P > 0.05), while endocan-MVD was associated with tumour size,Borrmann type, tumour differentiation, tumour invasion, lymph node metastasis and TNM stage(P < 0.05). According to the Spearman's rank correlation analysis, endocan-MVD had a positive correlation with VEGF(r = 0.167, P = 0.047) and VEGFR2(r = 0.410, P = 0.000). The univariate analysis with a log-rank test indicated that the patients with a high level of endocan-MVD had a significantly poorer overall survival rate than those with a low level of endocan-MVD(17.9% vs 64.0%, P = 0.000). The multivariate analysis showed that a high level of endocan-MVD was a valuable prognostic factor.CONCLUSION: Endocan-MVD significantly correlates with the expression of VEGF and VEGFR2 and is a valuable prognostic factor for survival in human gastric cancer.

Pancreaticoduodenectomy for duodenal papilla carcinoma: A single-centre 9-year retrospective study of 112 patients with long-term follow-up

AIM To retrospectively evaluate the factors that influence long-term outcomes of duodenal papilla carcinoma(DPC) after standard pancreaticoduodenectomy(SPD).METHODS This is a single-centre, retrospective study including 112 DPC patients who had a SPD between 2006 and 2015. Associations between serum levels of CA19-9 and CEA and various clinical characteristics of 112 patients with DPC were evaluated by the χ~2 test and Fisher's exact test. 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 60 mo(ranging from 4 mo to 168 mo). Survival analysis was conducted using the Kaplan-Meier survival and Cox proportional hazards model analysis. The difference in survival curves was evaluated with a log-rank test.RESULTS In 112 patients undergoing SPD, serum levels of CA19-9 was associated with serum levels of CEA and drainage mode(the P values were 0.000 and 0.033, respectively); While serum levels of CEA was associated with serum levels of CA19-9 and differentiation of the tumour(the P values were 0.000 and 0.033, respectively). The serum levels of CA19-9 and CEA were closely correlated(χ~2 = 13.277, r = 0.344, P = 0.000). The overall 5-year survival was 50.00% for 112 patients undergoing SPD. The Kaplan-Meier survival analysis showed that increased serum levels of CA19-9, CEA, and total bilirubin were correlated with a poor prognosis, as well as a senior grade of infiltration depth, lymph node metastases, and TNM stage(the P values were 0.033, 0.018, 0.015, 0.000, 0.000 and 0.000, respectively). Only the senior grade of infiltration depth and TNM stage retained their significance when adjustments were made for other known prognostic factors in Cox multivariate analysis(RR = 2.211, P = 0.022 and RR = 2.109, P = 0.047).CONCLUSION For patients with DPC, the serum levels of CA19-9 and CEA were closely correlated, and play an important role in poor survival. Increased serum levels of total bilirubin and lymph node metastases were also correlated with a poor prognosis. The senior grade of infiltration depth and TNM stage can serve as independent prognosis indexes in the evaluation of patients with DPC after SPD.