Purpose: Urothelial bladder cancer presents high recurrence rates, mandating continuous monitoring via invasive cystoscopy. The development of noninvasive tests for disease diagnosis and surveillance remains an unmet clinical need. In this study, validation of two urine-based biomarker panels for detecting primary and recurrent urothelial bladder cancer was conducted.Experimental Design: Two studies (total n ¼ 1,357) were performed for detecting primary (n ¼ 721) and relapsed urothelial bladder cancer (n ¼ 636). Cystoscopy was applied for detecting urothelial bladder cancer, while patients negative for recurrence had follow-up for at least one year to exclude presence of an undetected tumor at the time of sampling. Capillary electrophoresis coupled to mass spectrometry (CE-MS) was employed for the identification of urinary peptide biomarkers. The candidate urine-based peptide biomarker panels were derived from nested cross-sectional studies in primary (n ¼ 451) and recurrent (n ¼ 425) urothelial bladder cancer.Results: Two biomarker panels were developed on the basis of 116 and 106 peptide biomarkers using support vector machine algorithms. Validation of the urine-based biomarker panels in independent validation sets, resulted in AUC values of 0.87 and 0.75 for detecting primary (n ¼ 270) and recurrent urothelial bladder cancer (n ¼ 211), respectively. At the optimal threshold, the classifier for detecting primary urothelial bladder cancer exhibited 91% sensitivity and 68% specificity, while the classifier for recurrence demonstrated 87% sensitivity and 51% specificity. Particularly for patients undergoing surveillance, improved performance was achieved when combining the urine-based panel with cytology (AUC ¼ 0.87).Conclusions: The developed urine-based peptide biomarker panel for detecting primary urothelial bladder cancer exhibits good performance. Combination of the urine-based panel and cytology resulted in improved performance for detecting disease recurrence.
Genetic mutations appear to be additional risk factors for the development of thrombosis in patients with ALL. In contrast, these mutations do not appear to be relevant risk factors for thrombosis in the small number of children with other malignant diseases reported here. This difference may be due to asparaginase and corticosteroids being used in ALL but not in solid tumour protocols.
Purpose: To evaluate the diagnostic and prognostic performance of Secreted Protein Acidic and Rich in Cysteine (SPARC) in detecting urinary bladder cancer (UBC). Methods: The Integrated Study on Bladder Cancer (n = 571; mean age:69.4 ± 12.2 years) evaluates cross-sectionally SPARC diagnostic performance in primary (n = 264) and recurrent (n = 307) UBC. SPARC prognostic performance is evaluated in a nested cohort (n = 250) prospectively followed for 80 months to detect tumor relapse, recurrence and/or progression. Baseline urine samples are analyzed blindly using a commercially available SPARC ELISA assay, characterized for its analytical performance according to clinical test regulatory requirements (R&D Manufactures Inc.). Results: While higher mean SPARC levels are detected in primary (p = 0.008) and recurrent (p < 0.0001) UBC, the assay has limited diagnostic performance (AUC:0.593; 95% CI:0.524-0.663). SPARC positive patients undergoing disease monitoring are more likely to develop tumor relapse (age and gender Adj. HR:1.52; 95% CI:1.04-2.22) and progression (Adj. HR:1.83; 95% CI:1.02-3.27). However, prognostic performance is affected by hematuria. Conclusions: SPARC diagnostic performance for detecting UBC appears insufficient for clinical implementation. In patients undergoing disease monitoring, SPARC is a promising prognostic marker for tumor relapse and/or progression, but is affected by hematuria.
<p>Supplementary Table S6. Multivariate analysis for investigating the comparative performance of the biomarker classifier and cytology for detecting recurrence. Of the 211 subjects that were included in the validation phase, voided urinary cytology (VUC) results were available for 96 urinary samples.</p>
<p>Supplementary Table S4. Table summarizing the significant biomarkers that were revealed after statistical analysis between recurrent UBC cases (n=109) and negative for recurrence controls (n=316), using Wilcoxon test. The significant biomarkers were subsequently compared for their trend of regulation among the different centers, as shown in the second table sheet.</p>
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