DNA Methylation For Bladder Cancer Detection As Well As The 5-Fu Sensitivity Prediction In Breast Cancer

Objective This study aims to find some new DNA methylation markers in urine sediments to increase the specificity for detection of bladder cancer. Materials and Methods The promoter CpG Islands of the following ten genes that have been previously reported frequently hypermethylated in bladder cancer in the Western countries:CDH1,FANCF,LOXL1,LOXL4,P161NK4A,SFRP1, SOX9,TIG1,TIMP3 and XAF1 are subject to methylation specific PCR analysis in the DNA of 2 bladder cancer cell lines,2 normal bladder tissues and urine sediments of 82 bladder cancer patients,15 noncancerous urigenital patients and 5 healthy volunteers.Results Both XAF1 and LOXL1 were heterozygously methylated in the normal bladder tissues,showing no cancer state specificity.While the hypermethylated states were detected in urine sediments of bladder cancer at a frequency no less than 2.4%(2/82 cases),nine genes were also methylated in the patients of the noncancerous urigenital diseases.By a stringent statistic test,the methylated SFRP1 was detected in 36.6%(30/82 cases) of bladder cancer,including 50%(2/4 cases) of the stage 0a disease,indicating its potential clinical value for the detection of bladder cancer. Conclusions Inclusion of the methylated SFRP1 gene into a set of eleven genes that was previously reported by us for methylation profiling in urine sediments has improved the sensitivity of the bladder cancer detection.The insufficiency of predicting disease onset found with the previously recommended targets in the Western countries suggests a possible disease disparity between these two populations or the tissue specific methylation pattern that has been failed to be vigorously addressed in the previous studies as no non-cancerous samples had been recruited as a proper control.