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

Abstract

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.

Cross-Contamination of a UROtsa Stock with T24 Cells – Molecular Comparison of Different Cell Lines and Stocks

“…Urine (40 ml) was collected from four healthy donors. Cells from urine were harvested by centrifugation at 500× g for 10 min at 10°C [22].…”

Survinin expression in patients with breast cancer during chemotherapy

“…Disruption in the expression of survinin affects the tumorigenesis model, which suggests a central role of this protein in carcinogenesis and tumor progression [17]. Simultaneously, the relationship between overexpression of survinin and worse prognosis for patients with cancer was strengthened [11].…”

Chromosomal instability and bladder cancer: the UroVysionTM test in the UroScreen study

“…UroScreen was a prospective screening study in chemical workers aimed at assessing the predictive values of urinary tumour markers in detecting bladder cancer. The design and implementation of the study was described previously . In brief, participants were recruited from an established annual surveillance programme of the statutory accident insurance of the chemical industry.…”

“…The prospective study UroScreen was aimed at evaluating the performance of tumour markers for early detection of bladder cancer in chemical workers formerly exposed to carcinogenic aromatic amines . The results of the performance of the UroVysion test have been published elsewhere .…”