Correlation among VEGFR3 gene promoter methylation, protein overexpression, and clinical pathology in early gastric cancer.

BACKGROUND:The occurrence and development of gastric cancer is a multi-factor, multi-stage, multi-gene abnormal accumulation process. Both genetic and epigenetic mechanisms play an important role in the molecular mechanism of gastric cancer. DNA methylation is one of the most studied epigenetic expression mechanisms. To study the correlation between gene promoter methylation status and protein expression of vascular endothelial growth factor receptor 3 (VEGFR3), as well as their association with clinicopathological features in early gastric cancer (EGC) cases. METHODS:Immunohistochemical analysis and methylation-specific PCR (MSP) were used to detect the expression of VEGFR3 protein and methylation status of the VEGFR3 promoter in 50 cases of EGC and their paired normal gastric mucosa tissues. The level of DNA methylation of the VEGFR3 promoter, in situ VEGFR3 protein expression, and the clinicopathological characteristics of EGC patients were statistically analyzed. RESULTS:The positive rate of VEGFR3 protein expression in EGC tumor tissue (60%) was significantly higher than that in the normal gastric mucosa (10%). The detectable methylation frequency of VEGFR3 promoter in EGC tumor tissue (48%) was significantly lower than that in the normal gastric mucosa (85%). As anticipated, the methylation level of the VEGFR3 gene promoter was negatively associated with the overexpression of VEGFR3 protein. In addition, methylation status of the VEGFR3 gene promoter was positively correlated with lymph node metastasis in EGC patients (P<0.05), but was not linked to patients' gender, age, tumor size, degree of differentiation, or tumor invasion depth (P>0.05). CONCLUSIONS:Hypomethylation of the VEGFR3 gene promoter is one of the major mechanisms underlying VEGFR3 gene overexpression in EGC tumor tissues and is related to lymph node metastasis in EGC patients. DNA methylation of VEGFR3 is expected to become a molecular diagnostic and prognostic biomarker for EGC.