DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection

Negraes, Priscilla D.; Favaro, Francine Pinheiro; Camargo, João Lauro Viana de; Oliveira, Maria Luiza Cotrim Sartor de; Goldberg, José; Rainho, Cláudia Aparecida; Salvadori, Daisy Maria Fávero

doi:10.1186/1471-2407-8-238

Cited by 40 publications

(32 citation statements)

References 66 publications

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“…In this study, authors have investigated 2 DNA methylation biomarkers RARb 2 and APC (13), using MSP PCR (12), which can distinguish cytosine from methylated cytosine residues and can detect as few as 1 to 10 tumor cells among 10 Our results revealed significant urinary APC and RARb 2 promoter hypermethylation in malignant group as compared with benign and healthy normal groups confirming previous reports (13,23). The DNA hypermethylation of both genes was neither stage nor grade dependent, indicating that their usefulness is not limited to high-grade or high-stage tumors.…”

Section: Discussionsupporting

confidence: 76%

Aberrant Methylation ofRARβ2andAPCGenes in Voided Urine as Molecular Markers for Early Detection of Bilharzial and Nonbilharzial Bladder Cancer

Eissa

Swellam²,

El-Khouly³

et al. 2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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.

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Section: Discussionsupporting

confidence: 76%

Aberrant Methylation ofRARβ2andAPCGenes in Voided Urine as Molecular Markers for Early Detection of Bilharzial and Nonbilharzial Bladder Cancer

Eissa

Swellam²,

El-Khouly³

et al. 2011

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Our group also contributed to the literature surrounding epigenetic markers in bladder cancer. We discovered high rates of DNA methylation in exfoliated urinary cells, in which the RARB gene had a sensitivity of 95% and specificity of 71% for detecting the presence of cancer (Negraes et al, 2008). These results are concordant with the increased methylation frequencies that have been previously described (Chan et al, 2002;Hoque et al, 2006) and suggest that this gene could be considered as a diagnostic biomarker.…”

Section: Candidate Epigenetic Biomarkers In the Diagnosis Of Bladder supporting

confidence: 77%

Epigenetic Biomarkers in Bladder Cancer

Zimbardi¹,

Reis²,

Prando³

et al. 2012

Bladder Cancer - From Basic Science to Robotic Surgery

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“…However, most of these studies were based on qualitative rather than quantitative methods and the methylated gene promoters were typically identified in several types of urological tumors, thus hampering a differential detection of BlCa. The same approach has also been attempted in urine samples from BlCa patients but with essentially the same caveats and lower sensitivity (25)(26)(27)(28)(29)(30). Although marker specificity has been higher in most of these studies, the performance of the gene panels was not tested against other urological tumors and thus it is likely that specificity and positive predictive value would decrease.…”

Section: Discussionmentioning

confidence: 99%

Three Epigenetic Biomarkers, GDF15, TMEFF2, and VIM, Accurately Predict Bladder Cancer from DNA-Based Analyses of Urine Samples

Costa

Henrique

Danielsen

et al. 2010

Clinical Cancer Research

161

124

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Purpose: To identify a panel of epigenetic biomarkers for accurate bladder cancer (BlCa) detection in urine sediments.Experimental Design: Gene expression microarray analysis of BlCa cell lines treated with 5-aza-2 0 -deoxycytidine and trichostatin A as well as 26 tissue samples was used to identify a list of novel methylation candidates for BlCa. Methylation levels of candidate genes were quantified in 4 BlCa cell lines, 50 BlCa tissues, 20 normal bladder mucosas (NBM), and urine sediments from 51 BlCa patients and 20 healthy donors, 19 renal cancer patients, and 20 prostate cancer patients. Receiver operator characteristic curve analysis was used to assess the diagnostic performance of the gene panel.Results: GDF15, HSPA2, TMEFF2, and VIM were identified as epigenetic biomarkers for BlCa. The methylation levels were significantly higher in BlCa tissues than in NBM (P < 0.001) and the cancer specificity was retained in urine sediments (P < 0.001). A methylation panel comprising GDF15, TMEFF2, and VIM correctly identified BlCa tissues with 100% sensitivity and specificity. In urine samples, the panel achieved a sensitivity of 94% and specificity of 100% and an area under the curve of 0.975. The gene panel could discriminate BlCa from both healthy individuals and renal or prostate cancer patients (sensitivity, 94%; specificity, 90%).Conclusions: By using a genome-wide approach, we have identified a biomarker panel that allows for early and accurate noninvasive detection of BlCa using urine samples. Clin Cancer Res; 16(23); 5842-51. Ó2010 AACR.

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DNA methylation patterns in bladder cancer and washing cell sediments: a perspective for tumor recurrence detection

Abstract: Background: Epigenetic alterations are a hallmark of human cancer. In this study, we aimed to investigate whether aberrant DNA methylation of cancer-associated genes is related to urinary bladder cancer recurrence.

Cited by 40 publications

References 66 publications

Aberrant Methylation ofRARβ2andAPCGenes in Voided Urine as Molecular Markers for Early Detection of Bilharzial and Nonbilharzial Bladder Cancer

Aberrant Methylation ofRARβ2andAPCGenes in Voided Urine as Molecular Markers for Early Detection of Bilharzial and Nonbilharzial Bladder Cancer

Epigenetic Biomarkers in Bladder Cancer

Three Epigenetic Biomarkers, GDF15, TMEFF2, and VIM, Accurately Predict Bladder Cancer from DNA-Based Analyses of Urine Samples

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