Correlation Between Expression Of DCC Gene And Methylation Status Of DCC Gene Promoter In Clear Cell Renal Cell Carcinoma

Objective:To observe the expression of DCC (Deleted in Colorectal Carcinoma Gene) and the methylated rate of DCC promoter in ccRCC (Clear Cell Renal Cell Carcinoma) tissues and the corresponding non-cancerous tissues of ccRCC, and to investigate the potential correlation of DCC protein expression and the methylated rate of DCC promoter in ccRCC with clinicopathological features such as gender, age, pathological grade, clinical stage, tumor size, regional lymph node metastasis, distant metastasis and vascular infiltration and so on of ccRCC. And to further explore the relationship between the expression of DCC and the methylated rate of DCC promoter in ccRCC, so as to study the role of DCC in the development and progression of renal cell carcinoma and its possible molecular mechanisms clues.Methods:Immunohistochemical staining was performed on paraffin embedded sections of132cases of ccRCC and corresponding non-cancerous tissues to detect the expression of DCC, And Methylation specific PCR(MSP) was used to test the methylated rate of DCC promoter of50cases of ccRCC and corresponding non-cancerous tissues. The above results were statistically analyzed to determine whether the difference was statistically significant. And to further explore the potential correlation between the expression of DCC and the methylated rate of DCC promoter in ccRCC.Results:The positive rate39.39%(41/132) of DCC expression in ccRCC tissues was significantly lower than100%(0132/132) in corresponding non-cancerous tissues, and the difference was statistically significant (P＜0.05). The difference of DCC expression in ccRCC with gender, age, tumor size was not statistically significant (P>0.05), but the difference with pathological grade, clinical stage, regional lymph node metastasis,distant metastasis and vascular infiltration was statistically significant (P＜0.05). Log-rank displays that its survival difference was statistically significant (P=0.011). Further line COX univariate and multivariate analysis showed that: the expression of DCC, TNM stage, tumor grade, lymph node metastasis, distant metastasis and vascular invasion are all independent factors of ccRCC.The methylation rate of DCC in ccRCC tissues(39/50,78.0%) was higher than corresponding non-cancerous tissues(13/50,26.0%). The difference of methylation rate of DCC in ccRCC with gender, age, tumor size, and vascular infiltration was not statistically significant (P>0.05), but the difference with pathological grade, clinical stage, regional lymph node metastasis and distant metastasis was statistically significant (P<0.05).According to DCC expression weather or not,we divided ccRCC tissues and corresponding non-cancerous tissues into two groups.The methylation rate of DCC promoter in the group of DCC positive expression(10/20,50.0%) was siginificantly lower than that in the group of DCC negative expression(29/30,96.6%) in ccRCC tissues, and the difference was statistically significant (P＜0.05). And in the corresponding non-cancerous tissues, methylation rate of DCC promoter in the group of DCC positive expression was also siginificantly lower than that in the group of DCC negative expression, and the difference was statistically significant (P<0.05).Conclusions:The loss expression of DCC protein and the methylated higher rate of DCC promoter exactly existed in ccRCC and may accelerate the oncogenesis of ccRCC, In addition, loss of DCC expression the methylated higher rate of DCC promoter are related to the pathological grade, clinical stage, regional lymph node metastasis and distant metastasis of ccRCC, from what we can persume that loss of DCC expression and the methylated higher rate of DCC promoter may accelerate the invasion and metastasis of ccRCC.Connecting the methylation status of DCC promoter and the level of DCC expression, we find that DCC promoter methylation rate of DCC positive expression group is significantly higher than that of DCC negative expression group.These show that there is correlation between loss of DCC expression and DCC promoter methylation. Methylation of DCC promoter may be one of mechanisms about frequent loss of DCC expression in ccRCC.Our study may provide a new research direction to control the invasion and metastasis of malignant cells, and DCC may become a new target for treatment of tumor.