Clinical experience with survivin as a biomarker for urothelial bladder cancer

Horstmann, Marcus; Bontrup, Heike; Hennenlotter, Jörg; Taeger, Dirk; Weber, Anne M.; Pesch, Beate; Feil, G.; Patschan, Oliver; Johnen, Georg; Stenzl, Arnulf; Brüning, Thomas

doi:10.1007/s00345-010-0538-2

Cited by 44 publications

(27 citation statements)

References 17 publications

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“…Previously published studies showed specificities between 88% and 100% and sensitivities between 53% and 100% [28]–[30], [32]–[34]. While our results showed a similar specificity (98%) the sensitivity (21%) was markedly lower in this cohort study.…”

Section: Discussioncontrasting

confidence: 56%

“…Due to the fact that non-invasive detection in urine samples is possible, survivin could be used specifically for screening of urogenital malignancies. Several studies, mostly of cross-sectional design and with a relatively limited number of cases, have demonstrated that survivin is a promising candidate for further validation in longitudinal studies [28]–[34]. Shariat et al performed a larger prospective study on recurrent bladder cancer that was based on immunohistochemical staining of tumor samples.…”

Section: Introductionmentioning

confidence: 99%

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Performance of Survivin mRNA as a Biomarker for Bladder Cancer in the Prospective Study UroScreen

et al. 2012

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BackgroundUrinary biomarkers have the potential to improve the early detection of bladder cancer. Most of the various known markers, however, have only been evaluated in studies with cross-sectional design. For proper validation a longitudinal design would be preferable. We used the prospective study UroScreen to evaluate survivin, a potential biomarker that has multiple functions in carcinogenesis.Methods/ResultsSurvivin was analyzed in 5,716 urine samples from 1,540 chemical workers previously exposed to aromatic amines. The workers participated in a surveillance program with yearly examinations between 2003 and 2010. RNA was extracted from urinary cells and survivin was determined by Real-Time PCR. During the study, 19 bladder tumors were detected. Multivariate generalized estimation equation (GEE) models showed that β-actin, representing RNA yield and quality, had the strongest influence on survivin positivity. Inflammation, hematuria and smoking did not confound the results. Survivin had a sensitivity of 21.1% for all and 36.4% for high-grade tumors. Specificity was 97.5%, the positive predictive value (PPV) 9.5%, and the negative predictive value (NPV) 99.0%.ConclusionsIn this prospective and so far largest study on survivin, the marker showed a good NPV and specificity but a low PPV and sensitivity. This was partly due to the low number of cases, which limits the validity of the results. Compliance, urine quality, problems with the assay, and mRNA stability influenced the performance of survivin. However, most issues could be addressed with a more reliable assay in the future. One important finding is that survivin was not influenced by confounders like inflammation and exhibited a relatively low number of false-positives. Therefore, despite the low sensitivity, survivin may still be considered as a component of a multimarker panel.

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Section: Discussioncontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Performance of Survivin mRNA as a Biomarker for Bladder Cancer in the Prospective Study UroScreen

et al. 2012

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“…The reasons for study exclusion were as follows: other languages (six); review of literature (five) or editorial (one); report of previously reported data (one); required study design not met (five); other procedures (two); and other endpoint (two). Finally, 14 studies were included [14–27]. Two studies had two subsets of data [14,27].…”

Section: Resultsmentioning

confidence: 99%

Urine survivin as a diagnostic biomarker for bladder cancer: a systematic review

Godoy

Amiel

et al. 2012

BJU International

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What ' s known on the subject? and What does the study add? Although many tests for identifying patients with new or recurrent bladder cancer have been used, a reliable method has yet to be established. Recently, increasing attention has focused on the role of survivin in bladder cancer detection.Because urine survivin tests have better sensitivity than cytology, urine survivin could potentially replace routine cytology and might be used as an adjunct method for cystoscopy. However, the clinical utility of urine survivin as a bladder tumour marker identifi ed in the present study remains to be elucidated.To determine the clinical utility of urine survivin as a bladder tumour marker we systematically reviewed the available evidence. A comprehensive literature review was performed, from August 1997 to March 2011, using three search engines in English including PubMed, Cochrane Library, and SCOPUS. Two reviewers independently evaluated both trial eligibility and methodological quality and data extraction. We included studies that evaluated urine survivin, used cystoscopy and/or histopathology as the reference standard, and allowed the construction of a 2 × 2 contingency table. Bivariate random effect meta-analyses were used to calculate the summary estimated of sensitivity and specifi city and to construct a summary receiver-operating characteristics curve of urine survivin tests. In all, 14 studies were included in the present review; two studies had two subsets of data. There were 2051 subjects, including 1038 in the case group and 1013 in the control group, and heterogeneity was present among diagnostic studies. The pooled sensitivity and specifi city for urine survivin tests were 0.772 (95% confi dence interval [ CI ] 0.745 -0.797) and 0.918 (95% CI 0.899 -0.934), respectively. The area under the curve of urine survivin tests was 0.9392. When a subgroup analysis with six studies was performed, urine survivin tests had better sensitivity than cytology, but did not match cytology for specifi city. The clinical utility of urine survivin as a bladder tumour marker identifi ed in the present study remains to be elucidated.

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“…A protein survivin, which was upregulated in high-grade BC, could be shown to be downregulated in miR-1826 transfected BC cell lines. [2173] In the same study, three oncogenes, i.e., beta-catenin, mitogen-activated protein kinase 1, and vascular endothelial growth factor C were shown as targets of miR-1826, which was confirmed through Western blotting technique. [21] Limitations to miRNA-based cancer therapy such as unstable nature of miRNA, their rapid plasma clearance and poor uptake into the tumor cells are challenging.…”

Section: Bladder Cancer Biology and Micro Rnamentioning

confidence: 87%

Bladder cancer: Micro RNAs as biomolecules for prognostication and surveillance

et al. 2017

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Introduction:Bladder cancer (BC) has varied clinical behavior in terms of recurrence and progression. Current pathological characteristics are insufficient to prognosticate the outcome of a given treatment. Cellular metabolic regulatory molecules, such as micro RNA (miRNA), could be a potential biomarker to prognosticate the treatment outcomes.Materials and Methods:PubMed and Google Scholar databases were searched for publications from 1990 to 2016, related to miRNA biogenesis, its function, and role in the pathogenesis of bladder as well as other cancers. Articles were searched using MeSH terms micrornas, micrornas AND neoplasm, and micrornas AND urinary bladder neoplasm. Out of the 108 publications reviewed 75 references were selected based on the clinical relevance. Articles were reviewed to assess the role of miRNA in various cancers and those in BC as a diagnostic or therapeutic tool.Results:More than 35 miRNAs were found to be associated with different pathways of cellular dedifferentiation, proliferation, and progression of BC as well as other cancers. A normal looking mucosa may show molecular changes preceding phenotypic changes in the form of varied expression of miR-129, miR-200a, and miR-205. miR-214, miR-99a, and miR-125b have been shown to be potential urinary biomarkers of BC. miRNAs could act as a repressor for protein molecule functioning or activator of different pathways to be used as a therapeutic target too.Conclusions:Despite certain limitations, such as instability, rapid plasma clearance, and targeting antagonist proteins of cellular metabolic pathways, miRNAs have potential to be studied as a biomarker or a therapeutic target for BC.

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Clinical experience with survivin as a biomarker for urothelial bladder cancer

Abstract: In present group of patients, survivin was a reliable biomarker for high-grade urothelial BC (sensitivity 83%), but not for low grade (sensitivity 35%) urothelial BC with a high specificity (88%). No confounders influencing the results of survivin measurements could be identified.

Cited by 44 publications

References 17 publications

Performance of Survivin mRNA as a Biomarker for Bladder Cancer in the Prospective Study UroScreen

Performance of Survivin mRNA as a Biomarker for Bladder Cancer in the Prospective Study UroScreen

Urine survivin as a diagnostic biomarker for bladder cancer: a systematic review

Bladder cancer: Micro RNAs as biomolecules for prognostication and surveillance

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