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Background: Bladder cancer cells illustrate major disruptions in their DNA methylation patterns as compared with normal ones. Authors aimed to identify epigenetic molecular markers in urine for early detection of bladder cancer.Materials and Methods: We retrospectively analyzed the methylation status of RARb 2 and APC genes in urine samples from 210 bladder cancer patients, 61 patients with benign urological diseases, and 49 healthy volunteers by using methylation-specific PCR.Results: Methylated RARb 2 and APC were significantly higher in bladder cancer patients (62.8%, 59.5%) than benign (16.4%, 5%) but not detected in healthy volunteers (0%) at (P < 0.0001). Both methylated genes showed no significant difference among clinicopathologic factors; however, they were detected in all grades and stages. Among the 128 patients with bilharzial bladder cancer, 94 (73.4%) showed methylated RARb 2 and 86 (67.2%) showed methylated APC. Homoplasmic methylation pattern of both genes were only detected in bilharzial bladder cancer cases. Both sensitivities and specificities of the methylated genes for bladder cancer detection were superior to urine cytology and when altogether combined, the sensitivities improved to (91.8%), (93.5%), (91.9%), and (80.9%) in detection of: bladder cancer, non-muscle invasive bladder cancer, low-grade tumors, and bilharzial associated bladder cancer, respectively.Conclusion: Thus, methylated RARb 2 and APC genes might be valuable urinary molecular markers for early detection of bilharzial and nonbilharzial bladder cancer. Cancer Epidemiol Biomarkers Prev; 20(8); 1657-64. Ó2011 AACR.

This study was carried out to assess the efficacy of urinary hepatoma up-regulated protein (HURP) RNA in bladder cancer diagnosis and its relation to bilharziasis. Voided urine samples and blood were collected from 344 consecutive participants: 211 patients diagnosed with bladder cancer, 71 patients with benign urological disorders and 62 healthy volunteers. Serologic assessment of schistosomiasis antibody in sera, urine cytology and estimation of HURP RNA by reverse transcription polymerase chain reaction in urothelial cells was carried out in all samples. HURP RNA expression showed a significant difference among the three investigated groups. The best cutoff point for HURP RNA was determined as 0.0132 at 78.67 % sensitivity and 94 % specificity. The sensitivity of urine cytology was improved when combined with HURP RNA in detection of early stage (77.3 %), low grade (85.3 %) and bilharzial bladder cancer (78.1 %). Detection of urinary HURP RNA is a useful non-invasive test for early detection of bladder cancer and bilharzial bladder cancer and it improves sensitivity of urine cytology up to 91 %.

We sought to identify and validate a novel urinary autophagy transcript signature in patients with bladder cancer and evaluate its clinical utility. We performed an initial screening for seven autophagy transcript–based panel (autophagy-related protein 12 (ATG12); WD repeat domain, phosphoinositide interacting 2 (WIPI2); FYVE and coiled-coil domain-containing protein 1 (FYCO1); microtubule-associated protein light chain (MAPLC3); RB1-inducible coiled-coil 1 (RB1CC1); tachylectin-II-like beta-propeller domain 1 (TECPR1); and Unc-51-like kinase (ULK1)) that was identified based on bioinformatics analysis followed by SYBR Green–based polymerase chain reaction array validation in paired tissue and urine samples. Afterward, we evaluated the expression of differentially expressed autophagy transcripts in an independent validation set with reverse transcription quantitative real-time polymerase chain reaction in urine sediments of 140 patients with bladder cancer, 68 patients with benign urological lesions, and 74 healthy controls (age and sex matched). The expression levels of ATG12, FYCO1, TECPR1, and ULK1 in paired bladder tissue and urine samples were significantly lower in bladder cancer than in control group (p < 0.001). In the validation set, the receiver-operating characteristic curve analyses demonstrated that each urinary autophagy transcripts showed high sensitivity and specificity for distinguishing bladder cancer from non–bladder cancer patients (ATG12, 75.4% and 86.1%; FYCO1, 87% and 75.7%; ULK1, 85.5% and 75.6%; and TECPR1, 90% and 81.9%). We document and validate a novel autophagy transcript signature for human bladder cancer diagnosis: bilharzial and non-bilharzial types.

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