Developing biomarkers for improved diagnosis and treatment outcome monitoring of bladder cancer

Lintula, Susanna; Hotakainen, Kristina

doi:10.1517/14712598.2010.489546

Cited by 27 publications

(22 citation statements)

References 164 publications

(52 reference statements)

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“…Disease surveillance is cumbersome because of the invasive nature of cystoscopic examination and the low sensitivity of urinary cytology in the detection of low-grade tumors (7). Recently, efforts have been devoted to find better markers of disease diagnosis and prognosis in samples collected by noninvasive methods, such as urine sediments (8).…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…The majority of UBC are urothelial cell carcinomas (UCC) in Western countries, which include 90% or more of the cases, with the remaining comprising squamous cell carcinoma, adenocarcinoma, and other rare undifferentiated subtypes [9]. The natural history of UBC is complex and may involve divergent biological pathways, but two general forms are recognized: non-muscle invasive bladder cancer (NMIBC) and muscle-invasive form (MIBC).…”

Section: Introductionmentioning

confidence: 99%

Germline prognostic markers for urinary bladder cancer: Obstacles and opportunities

Chang

2012

Urologic Oncology: Seminars and Original Investigations

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Urinary bladder cancer is a heterogeneous disease with diverse genetic and environmental risk factors that can influence disease risk or clinical course for recurrence, progression, and survival. Therefore, identification of these factors is paramount for disease prevention and optimal clinical management of bladder cancer patients. Of particular interest is the need to identify molecular biomarkers that can give accurate assessment of tumor biological potential and to predict treatment response. Recent advances in molecular biology, cytogenetic and genomic research have spurred discovery efforts for novel genetic, epigenetic, and proteomic biomarkers that are prognostic for cancer. This review focuses on some of the important germline polymorphisms found to be correlated with clinical outcomes in bladder cancer. So far the majority of the identified candidate loci was based on prior knowledge of pathogenesis and had not been validated for clinical applications. The future challenges are to analyze the wealth of information from whole-genome studies, to understand the underlying biological mechanisms of these associations, the network of gene-gene and gene-environment interactions, and to apply these markers for the identification of high-risk population for targeted, personalized therapy.

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“…Recently, many urine-based protein biomarkers were implicated in identification of HG BC. But until now none of the molecular markers have been generally accepted in the clinical practice78. Therefore, the identification of objective and noninvasive biomarkers that could discriminate HG BC from LG BC or healthy control would be of considerable clinical value in individualized treatment and improvement of prognosis for BC.…”

mentioning

confidence: 99%

Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

Tan

Wang

Yuan

et al. 2017

Sci Rep

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To address the shortcomings of cystoscopy and urine cytology for detecting and grading bladder cancer (BC), ultrahigh performance liquid chromatography (UHPLC) coupled with Q-TOF mass spectrometry in conjunction with univariate and multivariate statistical analyses was employed as an alternative method for the diagnosis of BC. A series of differential serum metabolites were further identified for low-grade(LG) and high-grade(HG) BC patients, suggesting metabolic dysfunction in malignant proliferation, immune escape, differentiation, apoptosis and invasion of cancer cells in BC patients. In total, three serum metabolites including inosine, acetyl-N-formyl-5-methoxykynurenamine and PS(O-18:0/0:0) were selected by binary logistic regression analysis, and receiver operating characteristic (ROC) test based on their combined use for HG BC showed that the area under the curve (AUC) was 0.961 in the discovery set and 0.950 in the validation set when compared to LG BC. Likewise, this composite biomarker panel can also differentiate LG BC from healthy controls with the AUC of 0.993 and 0.991 in the discovery and validation set, respectively. This finding suggested that this composite serum metabolite signature was a promising and less invasive classifier for probing and grading BC, which deserved to be further investigated in larger samples.

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Developing biomarkers for improved diagnosis and treatment outcome monitoring of bladder cancer

Cited by 27 publications

References 164 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

Germline prognostic markers for urinary bladder cancer: Obstacles and opportunities

Three serum metabolite signatures for diagnosing low-grade and high-grade bladder cancer

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