| Objective: To investigate the correlation between VEGF or VEGFR2 expression with the clinic-pathologic characters as well as prognosis in gastric cancer patients; meanwhile, analyze the association among the VEGF or VEGFR2 expressing and IL-6/Stat3 signaling pathway, whose data obtained by other members of the team.Methods:(1) A total of 208(including 118 gastric cancer tissues and 90 paired adjacent normal tissues) surgically resected and paraffin-embedded archival tissues of human gastric cancer was obtained from the Department of Pathology, the First Affiliated Hospital of Shihezi University School of Medicine dated from 2004 to 2007. All the 118 patients were fully followed-up and the clinic-pathologic data were complete.(2) The patients were followed once a year, and the latest follow-up time was on October 1, 2014. The longest follow-up time was over 10 years.(3) The expression of VEGF and VEGFR2 were examined using immunohistochemistry on paraffin embedded tissue chips.(4) Statistical analyses were performed using the SPSS statistical software package(version 17.0). Nonparametric test was adopted for variance analysis, using Kaplan Meier method and Cox regression model analysis to evaluate the factors influencing patients’ prognosis, and correlations among those agents were analyzed using Spearman rank correlation method. Differences with P<0.05 were considered statistically significant.Results:(1) The VEGFR2 positive expression ratio in GC tissues is 75.4%(89/118), which is higher than the ANT tissues expression ratio 57.8%(52/90).However, the VEGF positive expression ratio in GC tissues is lower than the ANT tissues(74.6%, 88/118 vs 92.2%, 83/90).(2) In GC, the VEGF expression is correlated with the invasion depth(P=0.028), lympho node metastasis(P=0.012), distant metastasis(P=0.045) and clinical staging(P<0.001), but not age, sex and WHO classification(P>0.05). Similarly, the VEGFR2 expression is correlated with the male(P=0.014), lympho node metastasis(P<0.001), distant metastasis(P=0.011) and clinical staging(P<0.001), but not age, invasion depth and WHO classification(P>0.05).(3) Till the October 1, in 2014, 31(26.3%) gastric cancer patients were still alive, whereas 87(73.7%) had died. Follow-up ranged from 0 to 127 months and the median survival time was 24.5(40.8?38.2) months. The survival analysis reveal the high expression of VEGF or VEGFR2 correlated with the poor prognosis in GC.(4) The association among the VEGF or VEGFR2 expressing and IL-6/Stat3 signaling pathway display : both VEGF and VEGFR2 positive correlated with the expression of IL-6/Stat3 signaling pathway factors, such as: IL-6, Stat3, IL-17 A, IL-17F; and the strong positive association was observed between VEGF and VEGFR2(r=0.338); while, the negative correlation was observed between VEGF and SOCS3 expression.(5) Cox regression analysis shows that clinical staging is an independent risk factors affecting the prognosis of patients in gastric cancer.Conclusions:(1) The expression of VEGFR2 in GC tissues is higher than ANT tissues, and this study suggested that VEGFR2 may be more important than VEGF in the regulation of the role of angiogenesis in gastric carcinoma.(2) The high expressed VEGF and VEGFR2 correlated with the tumor growth and metastasis.(3) VEGF and VEGFR2 high expression correlated with the abnormal activation of Stat3 signal pathway, and indicate the patient may be late clinical staging, tumor metastasis or bad prognosis. |
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