Assessment of Hypermethylation of RASSF۱A and Protocadherin-۱۰ Tumor Suppressor Genes in Breast Cancer Females: A Six-Year Disease-Free Survival Case-Control Study

Background: This study intends to determine the diagnostic and prognostic roles of hypermethylation of serum RASSF۱A and protocadherin-۱۰ promoters in females with breast cancer.Methods: This study enrolled ۸۰ breast cancer patients and ۸۰ apparently normal healthy controls. The promoter methylation status of serum RASSF۱A and PCDH۱۰ genes was investigated using methylation specific PCR.Results: We detected no hypermethylation of the two genes in serum DNA of normal healthy controls (۱۰۰% specificity). Of the ۸۰ patients, ۵۰ (۶۲.۵% sensitivity) displayed hypermethylated RASSF۱A, whereas ۳۴ (۴۲.۵% sensitivity) showed hypermethylated PCDH۱۰ and ۶۴ (۸۰% sensitivity) were hypermethylated in at least one of these two genes. A significant association existed between hypermethylated RASSF۱A and axillary lymph node involvement. There was a significant association between hypermethylated PCDH۱۰ and axillary lymph node involvement, tumor size and pathological grade. Hypermethylated RASSF۱A and PCDH۱۰ combination was significantly associated with axillary lymph node involvement and Her-۲ expression. Patients with methylated RASSF۱A or PCDH۱۰ had significantly shorter survival rates compared to those with unmethylated RASSF۱A or PCDH۱۰.Conclusion:Methylated RASSF۱A is superior to methylated PCDH۱۰ for diagnosis of breast cancer patients. Addition of methylated PCDH۱۰ to methylated RASSF۱A significantly improves the diagnostic accuracy of RASSF۱A. The present study suggests that hypermethylated RASSF۱A and PCDH۱۰ may be independent prognostic indicators for disease-free survival in breast cancer patients.