Increase sensitivity in detecting superficial, low grade bladder cancer by combination analysis of hypermethylation of E-cadherin, p16, p14, RASSF1A genes in urine

Lin, Hui‐Hui; Ke, Hung‐Lung; Huang, Shu-Pin; Wu, Wen‐Jeng; Chen, Yu-Kuei; Chang, Lin‐Li

doi:10.1016/j.urolonc.2008.12.008

Cited by 59 publications

(37 citation statements)

References 21 publications

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“…In addition, some new investigational urine markers such as microsatellite alterations and gene mutations (e.g., fibroblast growth factor receptor 3; FGFR3) have not been widely deployed as a routine screening method for recurrence (30)(31)(32). Changes in DNA methylation are chemically stable, occur early during tumorigenesis, and can be quantified on high-throughput platforms, which make them poten- thereby establishing DNA methylation screening of urine sediments as a promising noninvasive approach for bladder cancer detection (10,19,21,(33)(34)(35)(36)(37). However, most studies have focused on finding correlations between the methylation status of markers present in the primary tumor or urine sediments at the time of diagnosis (before TURBT) and recurrence (38).…”

Section: Discussionmentioning

confidence: 99%

A Panel of Three Markers Hyper- and Hypomethylated in Urine Sediments Accurately Predicts Bladder Cancer Recurrence

Abreu

Chihara

et al. 2014

Clinical Cancer Research

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Purpose: The high risk of recurrence after transurethral resection of bladder tumor of nonmuscle invasive disease requires lifelong treatment and surveillance. Changes in DNA methylation are chemically stable, occur early during tumorigenesis, and can be quantified in bladder tumors and in cells shed into the urine. Some urine markers have been used to help detect bladder tumors; however, their use in longitudinal tumor recurrence surveillance has yet to be established.Experimental Design: We analyzed the DNA methylation levels of six markers in 368 urine sediment samples serially collected from 90 patients with noninvasive urothelial carcinoma (Tis, Ta, T1; grade lowhigh). The optimum marker combination was identified using logistic regression with 5-fold crossvalidation, and validated in separate samples.Results: A panel of three markers discriminated between patients with and without recurrence with the area under the curve of 0.90 [95% confidence interval (CI), 0.86-0.92] and 0.95 (95% CI, 0.90-1.00), sensitivity and specificity of 86%/89% (95% CI, 74%-99% and 81%-97%) and 80%/97% (95% CI, 60%-96% and 91%-100%) in the testing and validation sets, respectively. The three-marker DNA methylation test reliably predicted tumor recurrence in 80% of patients superior to cytology (35%) and cystoscopy (15%) while accurately forecasting no recurrence in 74% of patients that scored negative in the test.Conclusions: Given their superior sensitivity and specificity in urine sediments, a combination of hyperand hypomethylated markers may help avoid unnecessary invasive exams and reveal the importance of DNA methylation in bladder tumorigenesis. Clin Cancer Res; 20(7); 1978-89. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 99%

A Panel of Three Markers Hyper- and Hypomethylated in Urine Sediments Accurately Predicts Bladder Cancer Recurrence

Abreu

Chihara

et al. 2014

Clinical Cancer Research

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“…Hypermethlation of these genes was not not detected in any of the 20 urine samples from healthy control subjects. 107 These markers will require validation in future studies; however, urinary assays are currently being designed.…”

Section: Tumor Biology and Markersmentioning

confidence: 99%

Bladder Cancer in 2010: How Far have We Come?

Jacobs¹,

Lee

Montie

2010

CA: A Cancer Journal for Clinicians

295

275

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Bladder cancer is the fourth most common cancer and ranks eighth as a cause of death from cancer among men in the United States. Although guidelines assist in treatment, the art of managing bladder cancer, such as the decision to use neoadjuvant chemotherapy and the timing of cystectomy, is still variable. Bladder cancer has a propensity to recur, and with recurrence, a significant number of cases progress, which makes the early detection of high-risk patients imperative. Advances in detection, surveillance, and treatment of bladder cancer are reviewed in this article.

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“…Although the down-regulation of FHL1 has been found in several types of cancer (9-13), the expression level and molecular function of FHL1 in BC have not been clarified. Since many tumor suppressor genes silenced by DNA methylation have been identified in primary BC samples (14,15), we hypothesized that FHL1 expression is down-regulated by promoter hypermethylation in BC cells and that FHL1 functions as a tumor suppressor in BC cells.…”

Section: Discussionmentioning

confidence: 99%

“…Silencing of tumor suppressor genes by hypermethylation of CpG islands within the promoter and/or 5'-regions is a common feature of human cancer and is often associated with partial or complete transcriptional blocking. Many tumor suppressor genes silenced by DNA methylation have been identified in various types of cancer including BC (14,15). However, little is known about the status of FHL1 promoter methylation and the functional role of FHL1 in BC.…”

Section: Introductionmentioning

confidence: 99%

CpG hypermethylation of human four-and-a-half LIM domains 1 contributes to migration and invasion activity of human bladder cancer

Matsumoto

Kawakami²,

Enokida³

et al. 2010

Int J Mol Med

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Abstract. We previously reported a simple technique that combines microarray data from clinical bladder cancer (BC) specimens with those from a BC cell line (BOY) treated with a pharmacologic demethylating agent (5-aza-dC). We focused on the human four-and-a-half LIM domains 1 (FHL1) gene which was selected on the basis of previous microarray data analysis. Because LIM domains provide protein-protein binding interfaces, FHL genes play an important role in cellular events, such as focal adhesion and differentiation, by interacting with the target protein as either a repressor or activator. We hypothesized that inactivation of the FHL1 gene through CpG methylation contributes to cell viability including migration and invasion activity of human BC. After 5-aza-dC treatment, the expression levels of FHL1 mRNA transcript markedly increased in all cell lines tested, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR). The methylation index of FHL1 in our samples was significantly higher in 70 BC specimens than in 10 normal bladder epithelium (NBE) specimens (63.9±25.5 and 0.3±0.2, respectively; p=0.0066). Conversely, FHL1 mRNA expression was significantly lower in the BC specimens than in the NBE ones (0.331±0.12 and 2.498±0.61, respectively; p=0.0011). In addition, significant inhibitions of wound healing (45.78±6.2, and 100±0, respectively; p=0.009) and of cell invasion (18.5±2.3 and 95.2±2.4, respectively; p=0.02) were observed in stable FHL1-transfected cells than in the control BC cells. In conclusion, we found that the mechanism of FHL1 down-regulation in BC is through CpG hypermethylation of the promoter region. FHL1 gene inactivation by CpG hypermethylation may thus contribute to migration and invasion activity of BC.

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Increase sensitivity in detecting superficial, low grade bladder cancer by combination analysis of hypermethylation of E-cadherin, p16, p14, RASSF1A genes in urine

Cited by 59 publications

References 21 publications

A Panel of Three Markers Hyper- and Hypomethylated in Urine Sediments Accurately Predicts Bladder Cancer Recurrence

A Panel of Three Markers Hyper- and Hypomethylated in Urine Sediments Accurately Predicts Bladder Cancer Recurrence

Bladder Cancer in 2010: How Far have We Come?

CpG hypermethylation of human four-and-a-half LIM domains 1 contributes to migration and invasion activity of human bladder cancer

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