BackgroundProtein Tyrosine Phosphatase Receptor-type O (PTPRO) has recently been in the spotlight as a tumor suppressor, whose encoding gene is frequently methylated in cancers. We examined the methylation status of the PTPRO gene promoter in breast cancer and evaluated the correlation between PTPRO promoter methylation and both clinicopathological parameters and prognosis of breast cancer patients.MethodsTwo hundred twenty-one formalin-fixed, paraffin-embedded (FFPE) tumor tissues, 20 FFPE normal adjacent tissues and 24 matched plasma samples, collected from primary breast cancer patients, were assessed for PTPRO gene promoter methylation using methylation-specific PCR. Associations of promoter methylation with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect on survival.Results175 samples gave identifiable PCR products, of which 130 cases (74.3%) had PTPRO gene promoter methylation. PTPRO methylation correlated with higher histological grade (P = 0.028), but not other clinical parameters. Multivariate analysis indicated that overall survival (OS) was significantly poorer in HER2-positive, but not ER-positive patients with methylated-PTPRO. Methylated-PTPRO was detectable in matched plasma samples and only observed in plasma from patients whose corresponding primary tumors were also methylated.ConclusionsPTPRO methylation is a common event in the primary breast cancer and can be reliably detected in peripheral blood samples. PTPRO methylation is associated with poor survival only in HER2-positive patients, suggesting use of PTPRO methylation as a prognostic factor for breast cancer and for optimizing individualized therapy for HER2-positive patients.

ABSTRACT. Epigenetic inactivation of Ras-associated domain family 1A (RASSF1A) by hyper-methylation of its promoter region has been identified in various cancers. However, the role of RASSF1A in renal cancer has neither been thoroughly investigated nor reviewed. In this study, we reviewed and performed a meta-analysis of 13 published studies reporting correlations between methylation frequency of the RASSF1A promoter region and renal cancer risk. The odds ratios (ORs) of eligible studies and their corresponding 95% confidence intervals (95%CIs) were used to correlate RASSF1A promoter methylation with renal cell cancer risk and clinical or pathological variables, respectively. RASSF1A promoter methylation was significantly associated with the risk of renal cell cancer (OR = 19.35, 95%CI = 9.57-39.13). RASSF1A promoter methylation was significantly associated with pathological tumor grade (OR = 3.32, 95%CI = 1.55-7.12), and a possible positive correlation between RASSF1A promoter methylation status and tumor stage was noted (OR = 1.89, 95%CI = 1.00-3.56, P = 0.051). Overall, this meta-analysis demonstrated that RASSF1A promoter methylation is significantly associated with increased risk of renal cell cancer. RASSF1A promoter methylation frequency was positively correlated with pathological tumor grade, but not the clinical stage. This study showed that RASSF1A promoter methylation could be utilized to predict renal cell cancer prognosis.

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