UBC® Rapid Test—A Urinary Point-of-Care (POC) Assay for Diagnosis of Bladder Cancer with a focus on Non-Muscle Invasive High-Grade Tumors: Results of a Multicenter-Study

Ecke, Thorsten; Weiss, Sarah A.; Stephan, Carsten; Hallmann, S.; Arndt, Christian; Barski, Dimitri; Otto, T.; Gerullis, Holger

doi:10.3390/ijms19123841

Cited by 25 publications

(26 citation statements)

References 33 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Given that, none of the currently available urinary biomarkers that have been approved by the FDA can absolutely be recommended as a stand-alone test to replace cystoscopy in the clinic. Recently, several commercially available tests have been developed with improved sensitivity and specificity by using mRNA (e.g., "Xpert BC" [12]) or protein-based ELISA assay technology (e.g., "UBC" [13]), but these data must be independently be confirmed in further studies. Therefore, it is still of great interest to identify novel tumor biomarkers for urine-based early detection of bladder cancer, which might optimize existing panels and platforms to improve both the initial detection of bladder cancer and detection of its recurrence.…”

Section: Introductionmentioning

confidence: 99%

ITIH5 and ECRG4 DNA Methylation Biomarker Test (EI-BLA) for Urine-Based Non-Invasive Detection of Bladder Cancer

Rose

Bringezu

Godfrey

et al. 2020

IJMS

View full text Add to dashboard Cite

Bladder cancer is one of the more common malignancies in humans and the most expensive tumor for treating in the Unites States (US) and Europe due to the need for lifelong surveillance. Non-invasive tests approved by the FDA have not been widely adopted in routine diagnosis so far. Therefore, we aimed to characterize the two putative tumor suppressor genes ECRG4 and ITIH5 as novel urinary DNA methylation biomarkers that are suitable for non-invasive detection of bladder cancer. While assessing the analytical performance, a spiking experiment was performed by determining the limit of RT112 tumor cell detection (range: 100–10,000 cells) in the urine of healthy donors in dependency of the processing protocols of the RWTH cBMB. Clinically, urine sediments of 474 patients were analyzed by using quantitative methylation-specific PCR (qMSP) and Methylation Sensitive Restriction Enzyme (MSRE) qPCR techniques. Overall, ECRG4-ITIH5 showed a sensitivity of 64% to 70% with a specificity ranging between 80% and 92%, i.e., discriminating healthy, benign lesions, and/or inflammatory diseases from bladder tumors. When comparing single biomarkers, ECRG4 achieved a sensitivity of 73%, which was increased by combination with the known biomarker candidate NID2 up to 76% at a specificity of 97%. Hence, ITIH5 and, in particular, ECRG4 might be promising candidates for further optimizing current bladder cancer biomarker panels and platforms.

show abstract

Section: Introductionmentioning

confidence: 99%

ITIH5 and ECRG4 DNA Methylation Biomarker Test (EI-BLA) for Urine-Based Non-Invasive Detection of Bladder Cancer

Rose

Bringezu

Godfrey

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…A significant amount of recent biomarker research has been focused on aiding in the surveillance follow‐up of known bladder cancers 26–28 . Unfortunately, as biomarkers are often highly sensitive and can provide a positive result before it is cystoscopically visible, “anticipatory positive results,” the cost effectiveness of combined biomarker‐cystoscopy surveillance, have been shown to be worse than cystoscopy alone 26 .…”

Section: Discussionmentioning

confidence: 99%

The role of URO17™ biomarker to enhance diagnosis of urothelial cancer in new hematuria patients—First European Data

et al. 2020

View full text Add to dashboard Cite

Introduction and objectives Novel biomarker research is vital for the progression of safe and thorough diagnostic medicine. There is now a need to improve the diagnosis of bladder cancer via a noninvasive urine test while balancing the risks of harm from investigational procedures, such as cystoscopy and radiological tests, against the likelihood of malignancy. We evaluate the diagnostic accuracy and sensitivity of Uro17™ urinary biomarker for the detection of urothelial cancer in hematuria patients in a prospective blinded validation study. Uro17™ is an immunobiomarker which binds to the oncoprotein Keratin 17, which is involved in the replication cycle of malignant cells. This study compared cystoscopic and histological investigations against Uro17™ results in patients being investigated for symptoms of urothelial cancer. Materials and methods After receiving both local and national ethics/protocol approval, 71 patients were consented and recruited into the study. All patients were scheduled to undergo cystoscopic investigation, and following recruitment, a urine sample was collected. Urine samples were anonymized and processed as per standard cytology protocols and stained using Uro17™ immunobiomarker. The pathologists assessing the results were blinded to the patient and background history, and the results were compared to the biopsy histology. Results The full cohort of enrolled patients consisted of 71 participants included. There were 55 males and 16 females, with an average age of 70. Thirteen were current smokers, 42 ex‐smokers, and 16 nonsmokers. The malignancies detected included both muscle‐invasive (n = 6) and non‐muscle‐invasive tumors (n = 38), and tumors of all grades and carcinoma in situ. Uro17™ was shown to have an overall sensitivity of 100% and a specificity of 92.6%, with a positive predictive value of 0.957 and negative predictive value of 1. Uro17™ investigation was positive in every case of urothelial malignancy. Conclusions Our current data indicates Uro17™ is a highly sensitive noninvasive bladder cancer urine detection test that can improve the diagnosis of Bladder cancer. This can further improve diagnostic capabilities in primary care, reduce the number of referrals to Urology department, and reduce the number of unnecessary invasive procedures for new patients with a suspected urinary bladder cancer.

show abstract

“…With respect to quantitative assay determinations, cytokeratin levels are lower in low-grade tumors and benign urological diseases, compared to high-grade tumors [ 1 , 2 ]. Recent investigations including sensitivity–specificity characteristic (SS-ROC) curves gave evidence of utility for the UBC ® Rapid Test in detecting CIS (carcinoma in situ) and non-invasive high-risk tumors [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Establishment and Characterization of an Empirical Biomarker SS/PV-ROC Plot Using Results of the UBC® Rapid Test in Bladder Cancer

Oehr

Ecke

2020

Entropy

Self Cite

View full text Add to dashboard Cite

Background: This investigation included both a study of potential non-invasive diagnostic approaches for the bladder cancer biomarker UBC® Rapid Test and a study including comparative methods about sensitivity–specificity characteristic (SS-ROC) and predictive receiver operating characteristic (PV-ROC) curves that used bladder cancer as a useful example. Methods: The study included 289 urine samples from patients with tumors of the urinary bladder, patients with non-evidence of disease (NED) and healthy controls. The UBC® Rapid Test is a qualitative point of care assay. Using a photometric reader, quantitative data can also be obtained. Data for pairs of sensitivity/specificity as well as positive/negative predictive values were created by variation of threshold values for the whole patient cohort, as well as for the tumor-free control group. Based on these data, sensitivity–specificity and predictive value threshold distribution curves were constructed and transformed into SS-ROC and PV-ROC curves, which were included in a single SS/PV-ROC plot. Results: The curves revealed TPP-asymmetric improper curves which cross the diagonal from above. Evaluation of the PV-ROC curve showed that two or more distinct positive predictive values (PPV) can correspond to the same value of a negative predictive value (NPV) and vice versa, indicating a complexity in PV-ROC curves which did not exist in SS-ROC curves. In contrast to the SS-ROC curve, the PV-ROC curve had neither an area under the curve (AUC) nor a range from 0% to 100%. Sensitivity of the qualitative assay was 58.5% and specificity 88.2%, PPV was 75.6% and NPV 77.3%, at a threshold value of approximately 12.5 µg/L. Conclusions: The SS/PV-ROC plot is a new diagnostic approach which can be used for direct judgement of gain and loss of predictive values, sensitivity and specificity according to varied threshold value changes, enabling characterization, comparison and evaluation of qualitative and quantitative bioassays.

show abstract

UBC® Rapid Test—A Urinary Point-of-Care (POC) Assay for Diagnosis of Bladder Cancer with a focus on Non-Muscle Invasive High-Grade Tumors: Results of a Multicenter-Study

Cited by 25 publications

References 33 publications

ITIH5 and ECRG4 DNA Methylation Biomarker Test (EI-BLA) for Urine-Based Non-Invasive Detection of Bladder Cancer

ITIH5 and ECRG4 DNA Methylation Biomarker Test (EI-BLA) for Urine-Based Non-Invasive Detection of Bladder Cancer

The role of URO17™ biomarker to enhance diagnosis of urothelial cancer in new hematuria patients—First European Data

Establishment and Characterization of an Empirical Biomarker SS/PV-ROC Plot Using Results of the UBC® Rapid Test in Bladder Cancer

Contact Info

Product

Resources

About