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Purpose    Schistosoma haematobium  is associated with chronic bladder damage and may subsequently induce bladder cancer in humans, thus posing a serious threat where the parasite is endemic. Here we evaluated aberrant promoter DNA methylation as a potential biomarker to detect severe bladder damage that is associated with schistosomiasis by analyzing urine specimens.    Materials and Methods  A quantitative methylation-specific PCR (QMSP) assay was used to examine the methylation status of seven genes ( RASSF1A, RARβ2, RUNX3, TIMP3, MGMT, P16, ARF ) in 57 urine samples obtained from volunteers that include infected and uninfected by  S. haematobium  from an endemic region. The Fishers Exact Test and Logistic Regression analysis were used to evaluate the methylation status with bladder damage (as assessed by ultrasound examination) in subjects with  S. haematobium  infection.    Results    RASSF1A  and  TIMP3  were significant to predict severe bladder damage both in univariate (p = 0.015 and 0.023 respectively) and in multivariate (p = 0.022 and 0.032 respectively) logistic regression analysis. Area under the receiver operator characteristic curves (AUC-ROC) for  RASSF1A  and  TIMP3  to predict severe bladder damage were 67.84% and 63.73% respectively. The combined model, which used both  RASSF1A  and  TIMP3  promoter methylation, resulted in significant increase in AUC-ROC compared to that of  TIMP3  (77.55% vs. 63.73%.29; p = 0.023).    Conclusions  In this pilot study, we showed that aberrant promoter methylation of  RASSF1A  and  TIMP3  are present in urine sediments of patients with severe bladder damage associated with  S. haematobium  infection and that may be used to develop non-invasive biomarker of  S. haematobium  exposure and early molecular risk assessmentof neoplastic transformation.

Hypermethylation of Genes Detected in Urine from Ghanaian Adults with Bladder Pathology Associated with Schistosoma haematobium Infection