Aberrant Promoter Methylation Of SFRPs-the Antagonists Of Wnt In Renal Cell Carcinoma

Objective:Renal cell carcionma is one of the most common malignant tumors and the incidence rate ranks the second place in the urinary system , accounting for about 2% to 3% of all over the body. The pathogenesis mechasim of renal cell carcinoma is unknown , in addition to genetic factors , the known risk factors are smoking, obesity, industry, water pollution, radiation and so on. The disease incidence is convert, and when symptoms appeared the stage is advanced. It is necessary to detect its pathogenesis to reduce the renal carcinoma morbidity and mortality.Recently, the DNA methylation has been the focus concerned widespread. The purpose of this research is to investigate the methylation of gene SFRP1, SFRP2, SFRP4 and SFRP5 in renal cell carcinoma and corresponding normal tissues to explore the relationship between gene methylation and the occurrence of renal cell carcinoma, invasion, metastasis and pathological differentiation of RCC to provide a new theory and evidence for pathogenesy, gene therapy and immunotherapy, clinical prognosis of the renal cell carcinoma.Methods:1 The CpG-island methylation in SFRP1, SFRP2, SFRP4, SFRP5 gene were detected by methylation-specific polymerase chain reaction (MSP).2 SPSS13.0 was applied to analyze the data of experiment.Results:1 Analyze the SFRP1 gene methylation and its relationship with the incidence of clinical and pathological data.The methylation rate of the renal cell carcinoma and corresponding normal tissues were 77.3% (51/66)and 30.0% (9/30) respectively. Methylation frequencies of the SFRP1 gene in renal cell carcinoma increased significantly compared with adjacent non-tumor tissues (P<0.001); Methylation frequencies of SFRP1 gene in clinical stageâ… ,â…¡69.6%(32/46)was significantly lower than that of III,â…£95.0% (19/20) (P=0.027); Methylation frequencies of SFRP1 gene in poor differentiation group 83.3% (15/18) was higher than moderate and poor-moderate differentiation groups 75.0% (36/48) , but did not have significant difference (P>0.05); Methylation frequencies of SFRP1 gene in the group of less than 60-year-old 80.6%(29/36)was more than the group of greater than or equal 60-year-old 73.3 (22/30), The methylation rate of the men and women were 75.5%, 82.4%, respectively but there was no significance (P>0.05).2 Analyze the SFRP2 gene methylation and its relationship with the incidence of clinical and pathological data.SFRP2 gene was methylated in 48 of 66 (72.7%) tumor specimens, which was significantly higher than that in corresponding normal tissues 46.7% (14/30) (P=0.013); Methylation frequencies of SFRP2 gene in clinical stageâ… ,â…¡67.4%(31/46)was significantly lower than that III,â…£85.0% (17/20)(P>0.05); Methylation frequencies of SFRP2 gene in moderate and poor-moderate differentiation group 68.8% (33/48) was lower than poor differentiation groups 83.3% (15/18) , but did not show significant difference (P>0.05); Methylation frequencies of SFRP2 gene had difference in different age and gender groups, but there was no significance (P>0.05).3 Analyze the SFRP4 gene methylation and its relationship with the incidence of clinical and pathological data.The methylation rate of the renal cell carcinoma and corresponding normal tissues were 59.1% (39/66) and 13.3% (4/30). Methylation frequencies of the SFRP4 gene in renal cell carcinoma was significantly higher than corresponding normal tissues (P<0.001); Methylation frequencies of SFRP2 gene in moderate and poor-moderate differentiation group 45.8% (22/48) was significantly lower than poor differentiation groups 94.4% (17/18) (P<0.001); Methylation frequencies of SFRP4 gene in clinical stageâ… ,â…¡52.2%(24/46)was lower than that III,â…£75.0% (15/20) (P>0.05); Methylation frequencies of SFRP4 gene had difference in different age and gender groups, but there was no significance (P>0.05).4 Analyze the SFRP5 gene methylation and its relationship with the Incidence of clinical and pathological data.SFRP5 gene was methylated in 46 of 66 (69.7%) tumor specimens, which was significantly higher than that in corresponding normal tissues 36.7% (11/30)(P=0.002); Methylation frequencies of SFRP5 gene in clinical stageâ… ,â…¡60.9%(28/46)was lower than that III,â…£90.0% (18/20)(P=0.018); Methylation frequencies of SFRP5 gene in poor differentiation group77.8% (14/18) was higher than moderate and poor-moderate differentiation groups 66.7% (32/48) (P>0.05); Methylation frequencies of SFRP5 gene had difference in different age and gender groups, but there was no significance (P>0.05).Conclusions:1 The methylation frequencies of SFRP1, SFRP2, SFRP4 and SFRP5 in renal cell carcinoma were all significantly higher than that in corresponding normal tissues, suggesting that the methylation of SFRP1, SFRP2, SFRP4 and SFRP5 gene may be related to the occurrence of renal cell carcinoma.2 The higher methylation frequencies of SFRP1 and SFRP5, suggesting that SFRP1, SFRP5 may be related to the development of renal cell carcinoma, invasion, metastasis. Methylation frequencies of SFRP4 gene in moderate and poor-moderate differentiation group was significantly lower than that in poor differentiation groups, which indicate that SFRP4 may related to the malignant behavior of renal cell carcinoma.