VEGF rs3025039和rs3025021多态性与胃癌组织中VEGF、COX-2表达的关系

Association of VEGF rs3025039 and rs3025021 with VEGF and COX-2 expression in gastric cancer tissues

目的研究血管内皮生长因子(VEGF)基因单核甘酸多态性与安徽地区胃癌易感性关系以及与胃癌临床病理特征和胃癌组织VEGF、环氧化酶-2(COX-2)蛋白表达的关系。方法采用基因测序仪对安徽地区238例胃癌患者及425例正常对照组血样进行VEGF rs3025039和rs3025021的多态性测序,用组织芯片技术及免疫组化法检测相应胃癌组织和30例癌旁组织中VEGF和COX-2的分布。结果与正常对照相比,胃癌患者VEGF rs3025039TT基因型可能增加胃癌风险性(P=0.047,OR=2.86,95%CI=1.01～8.08)。rs3025021CT基因型显著降低胃癌风险性(P=0.032,OR=0.65,95%CI=0.44～0.96)。胃癌组织VEGF和COX-2的阳性率分别为62.6%及61.8%,显著高于癌旁组织的26.7%(P=0.000)和36.7%(P=0.008),并与TNM分期、肿瘤大小、浸润深度、淋巴结转移、临床分期(仅VEGF)及组织学类型(仅COX-2)有关(P=0.001～0.05)。VEGF表达与COX-2呈正相关(rs=0.178,P=0.006)。除VEGF rs3025021与肿瘤大小有关(P=0.026)外,VEGF rs3025039和rs3025021与胃癌临床病理学参数及VEGF及COX-2表达均无关。结论VEGF rs3025039和rs3025021多态性影响安徽地区的胃癌易感性,对胃癌组织VEGF表达无明显影响;VEGF及COX-2表达与胃癌的肿瘤侵袭性密切相关,二者对胃癌的恶化进展可能有一定的协同作用。

Purpose To explore the correlation between the single nucleotide polymorphisms（SNPs） of VEGF and susceptibility of gastric cancer in Anhui region,and to investigate the relationship among SNPs in VEGF gene,clinicalpathological parameters and expression of vascular endothelial growth factor（VEGF） and cyclooxygenase-2（COX-2） in gastric cancer tissues.Methods VEGF rs3025039 and rs3025021 in 238 patients with gastric cancer and 425 controls from Anhui Province were genotyped by using gene sequencing instrument.Expression of VEGF and COX-2 in 238 cases of gastric cancers and 30 adjacent noncancerous tissues of the patients were detected by tissue microarray-based immunohistochemistry.Results VEGF rs3025039TT and rs3025021CT genotype significantly increased or decreased the risk of gastric cancer（P=0.047,OR=2.86,95% CI=1.01～8.08;P=0.032,OR=0.65,95% CI=0.44～0.96,respectively）.Gastric cancers revealed significant expression of both VEGF and COX-2（62.6% and 61.8%,respectively） compared to the adjacent tissues（26.7% with P=0.000 and 36.7% with P=0.008,respectively）.There were statistically significant correlations of the expression of VEGF and COX-2 to tumor biological behaviors of gastric cancers： clinical TNM stage,tumor size,invasive depth,lymph node metastasis,clinical stage（only VEGF） and histological type（only COX-2）（P=0.001～0.05）.Expression of VEGF was positively correlated with that of COX-2（rs=0.178,P=0.006）.There were no relationship among VEGF gene polymorphisms,clinicopathological parameters and expression of VEGF and COX-2 in gastric cancer tissues,excepting that VEGF rs3025021 was significantly correlated with tumor size（P=0.026）.Conclusions VEGF rs3025039 and rs3025021 polymorphisms affect the susceptibility of gastric cancer in Anhui region,but do not correlate with the expression of VEGF.The two proteins of VEGF and COX-2 are strongly associated with the invasion of gastric cancer,and might play a synergistic role in the progress of gastric cancers.