Detection of aberrantly methylated tumor suppressor genes in breast cancer patients as a potential diagnostic biomarker

Abstract Background: Aberrant methylation of tumor suppressor genes is a common feature of breast cancer. Identifying a panel of methylated genes that are sensitive and specific for breast cancer could help to diagnose and predict prognosis of breast cancer.Methods: We determined the methylation status of DACT1, PAX5, PLCD1, ZNF545 and TET1 in 32 benign controls, 237 cancer tissue samples and 33 paired plasma samples.Results: PAX5 and PLCD1 showed exceedingly high methylation rates with percentages of 69.2% and 54.9%, whereas the methylation percentage of DACT1, ZNF545 and TET1 were 33.8%, 28.7% and 18.2% in cancer samples, respectively. A better survival of patients with ZNF545 methylation (p = 0.0350) was detected. Correlation of promoter methylation and clinicopathological features in 32 individuals with benign disease and 237 cancer patients demonstrated that methylated status of DACT1 (p=0.012), PLCD1 (p=0.013), and ZNF545 (p=0.012) had significant difference in age, and the methylation of PAX5 (p=0.006) was correlated with absence of hormone receptors, which implied an adverse outcome. PAX5 and PLCD1 both had high sensitivity (69.20% and 54.85%, respectively) and high specificity (87.50% and 100.00%, respectively). Patients with methylation of PAX5 likely to have a higher risk of breast cancer (OR=15.726, 95% CI=5.323-46.463, p<0.001), and statistical analysis of public online database showed the similar results. Conclusion: PAX5, PLCD1, ZNF545 and TET1 may serve as new potential diagnostic and prognostic biomarkers for breast cancer.