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  1. Article ; Online: Establishment and Characterization of an Empirical Biomarker SS/PV-ROC Plot Using Results of the UBC ® Rapid Test in Bladder Cancer

    Peter Oehr / Thorsten Ecke

    Entropy, Vol 22, Iss 729, p

    2020  Volume 729

    Abstract: 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 ... ...

    Abstract 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.
    Keywords predictive ROC curve ; ROC curve ; PV-ROC curve ; SS-ROC curve ; SS/PV-ROC plot ; empirical ; Science ; Q ; Astrophysics ; QB460-466 ; Physics ; QC1-999
    Subject code 516
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Book ; Online: Diagnostic, Prognostic and Predictive Biological Markers in Bladder Cancer – Illumination of a Vision

    Thorsten Ecke (Ed.) / Thomas Otto (Ed.)

    2019  

    Abstract: This Special Issue has been introduced with the aim of offering the possibility to publish new research results from old and new pioneers in the field of bladder cancer basic research. While editing this Special Issue we learned that an enormous ... ...

    Abstract This Special Issue has been introduced with the aim of offering the possibility to publish new research results from old and new pioneers in the field of bladder cancer basic research. While editing this Special Issue we learned that an enormous enthusiasm is necessary to go on in bladder cancer research. In our eyes, bladder cancer is on one hand a very heterogenous malignancy, which is what makes it so difficult to focus on only one bladder cancer marker in bladder cancer diagnostics and follow-up. On the other hand, it is very important to find prognostic and predictive factors for bladder cancer due to its high incidence and its enormous costs, as one of the most expensive malignancies in the world. Finding and developing new bladder cancer markers is still a very dynamic field. Because there are many of these markers, it is impossible to report all of them. This Special Issue attempts to highlight the role of bladder cancer markers in diagnosis, and the most important biomarkers that have been recently studied and reported. This Special Issue highlights some of the most important markers. Further determination of recurrence and progression markers will contribute to establishing better treatments for individual patients. Molecular staging of urological tumors will allow the selection of cases that will require systemic treatment. It is necessary and important to integrate basic and clinical research under the same objectives.
    Keywords Bladder cancer ; diagnostics ; tumor markers ; molecular biology
    Subject code 616
    Language English
    Publisher MDPI - Multidisciplinary Digital Publishing Institute
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Exploring solid-phase proximity ligation assay for survivin detection in urine.

    Jan Gleichenhagen / Christian Arndt / Swaantje Casjens / Carmen Töpfer / Holger Gerullis / Irina Raiko / Dirk Taeger / Thorsten Ecke / Thomas Brüning / Georg Johnen

    PLoS ONE, Vol 17, Iss 6, p e

    2022  Volume 0270535

    Abstract: Urine-based biomarkers are a rational and promising approach for the detection of bladder cancer due to the proximity of urine to the location of the tumor site and the non-invasive nature of its sampling. A well-known and highly investigated biomarker ... ...

    Abstract Urine-based biomarkers are a rational and promising approach for the detection of bladder cancer due to the proximity of urine to the location of the tumor site and the non-invasive nature of its sampling. A well-known and highly investigated biomarker for bladder cancer is survivin. For detection of very small amounts of urinary survivin protein a highly sensitive assay was developed. The assay is based on the immuno-PCR technology, more precisely a solid-phase proximity ligation assay (spPLA). The limit of detection for the survivin spPLA was 1.45 pg/mL, resulting in an improvement of the limit of detection by a factor of approximately 23 compared to the previously in-house developed survivin ELISA. A key step in development was the initial isolation of survivin by a molecular fishing rod based on magnetic beads. Interfering matrix compounds pose a special challenge for further analytical application, but can be overcome by this isolation step. The assay is designed to work with only 500 μL of voided urine. The survivin spPLA showed a sensitivity of 30% and specificity of 89% for bladder cancer detection in this study of 110 bladder cancer cases and 133 clinical controls. Moreover, the results demonstrated again that survivin is a useful complementary marker in combination with UBC® Rapid by increasing the overall sensitivity to 70% with a specificity of 86%. Although the performance for detection of bladder cancer was rather low, the herein developed assay might serve as a new tool for survivin biomarker research in diverse human fluids, even if the biological matrix is complex or survivin is only present in small amounts.
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Evaluation of a New Survivin ELISA and UBC® Rapid for the Detection of Bladder Cancer in Urine

    Jan Gleichenhagen / Christian Arndt / Swaantje Casjens / Carmen Meinig / Holger Gerullis / Irina Raiko / Thomas Brüning / Thorsten Ecke / Georg Johnen

    International Journal of Molecular Sciences, Vol 19, Iss 1, p

    2018  Volume 226

    Abstract: Urine-based biomarkers for non-invasive diagnosis of bladder cancer are urgently needed. No single marker with sufficient sensitivity and specificity has been described so far. Thus, a combination of markers appears to be a promising approach. The aim of ...

    Abstract Urine-based biomarkers for non-invasive diagnosis of bladder cancer are urgently needed. No single marker with sufficient sensitivity and specificity has been described so far. Thus, a combination of markers appears to be a promising approach. The aim of this case-control study was to evaluate the performance of an in-house developed enzyme-linked immunosorbent assay (ELISA) for survivin, the UBC® Rapid test, and the combination of both assays. A total of 290 patients were recruited. Due to prior bladder cancer, 46 patients were excluded. Urine samples were available from 111 patients with bladder cancer and 133 clinical controls without urologic diseases. Antibodies generated from recombinant survivin were utilized to develop a sandwich ELISA. The ELISA and the UBC® Rapid test were applied to all urine samples. Receiver operating characteristic (ROC) analysis was used to evaluate marker performance. The survivin ELISA exhibited a sensitivity of 35% with a specificity of 98%. The UBC® Rapid test showed a sensitivity of 56% and a specificity of 96%. Combination of both assays increased the sensitivity to 66% with a specificity of 95%. For high-grade tumors, the combination showed a sensitivity of 82% and a specificity of 95%. The new survivin ELISA and the UBC® Rapid test are both able to detect bladder cancer, especially high-grade tumors. However, the performance of each individual marker is moderate and efforts to improve the survivin assay should be pursued. A combination of both assays confirmed the benefit of using marker panels. The results need further testing in a prospective study and with a high-risk population.
    Keywords survivin ; UBC® Rapid ; bladder cancer ; urine ; biomarker combination ; non-invasive ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  5. Article ; Online: Activating Telomerase TERT Promoter Mutations and Their Application for the Detection of Bladder Cancer

    Maria Zvereva / Eduard Pisarev / Ismail Hosen / Olga Kisil / Simon Matskeplishvili / Elena Kubareva / David Kamalov / Alexander Tivtikyan / Arnaud Manel / Emmanuel Vian / Armais Kamalov / Thorsten Ecke / Florence Le Calvez-Kelm

    International Journal of Molecular Sciences, Vol 21, Iss 6034, p

    2020  Volume 6034

    Abstract: This review summarizes state-of-the-art knowledge in early-generation and novel urine biomarkers targeting the telomerase pathway for the detection and follow-up of bladder cancer (BC). The limitations of the assays detecting telomerase reactivation are ... ...

    Abstract This review summarizes state-of-the-art knowledge in early-generation and novel urine biomarkers targeting the telomerase pathway for the detection and follow-up of bladder cancer (BC). The limitations of the assays detecting telomerase reactivation are discussed and the potential of transcription-activating mutations in the promoter of the TERT gene detected in the urine as promising simple non-invasive BC biomarkers is highlighted. Studies have shown good sensitivity and specificity of the urinary TERT promoter mutations in case-control studies and, more recently, in a pilot prospective cohort study, where the marker was detected up to 10 years prior to clinical diagnosis. However, large prospective cohort studies and intervention studies are required to fully validate their robustness and assess their clinical utility. Furthermore, it may be interesting to evaluate whether the clinical performance of urinary TERT promoter mutations could increase when combined with other simple urinary biomarkers. Finally, different approaches for assessment of TERT promoter mutations in urine samples are presented together with technical challenges, thus highlighting the need of careful technological validation and standardization of laboratory methods prior to translation into clinical practice.
    Keywords bladder cancer ; biomarkers ; non-invasive detection ; telomerase ; somatic mutations ; TERT promoter region ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 616
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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  6. Article ; Online: Immunological tumor status may predict response to neoadjuvant chemotherapy and outcome after radical cystectomy in bladder cancer

    Minna Tervahartiala / Pekka Taimen / Tuomas Mirtti / Ilmari Koskinen / Thorsten Ecke / Sirpa Jalkanen / Peter J. Boström

    Scientific Reports, Vol 7, Iss 1, Pp 1-

    2017  Volume 9

    Abstract: Abstract Bladder cancer (BC) is the ninth most common cancer worldwide. Radical cystectomy (RC) with neoadjuvant chemotherapy (NAC) is recommended for muscle-invasive BC. The challenge of the neoadjuvant approach relates to challenges in selection of ... ...

    Abstract Abstract Bladder cancer (BC) is the ninth most common cancer worldwide. Radical cystectomy (RC) with neoadjuvant chemotherapy (NAC) is recommended for muscle-invasive BC. The challenge of the neoadjuvant approach relates to challenges in selection of patients to chemotherapy that are likely to respond to the treatment. To date, there are no validated molecular markers or baseline clinical characteristics to identify these patients. Different inflammatory markers, including tumor associated macrophages with their plastic pro-tumorigenic and anti-tumorigenic functions, have extensively been under interests as potential prognostic and predictive biomarkers in different cancer types. In this immunohistochemical study we evaluated the predictive roles of three immunological markers, CD68, MAC387, and CLEVER-1, in response to NAC and outcome of BC. 41% of the patients had a complete response (pT0N0) to NAC. Basic clinicopathological variables did not predict response to NAC. In contrast, MAC387+ cells and CLEVER-1+ macrophages associated with poor NAC response, while CLEVER-1+ vessels associated with more favourable response to NAC. Higher counts of CLEVER-1+ macrophages associated with poorer overall survival and CD68+ macrophages seem to have an independent prognostic value in BC patients treated with NAC. Our findings point out that CD68, MAC387, and CLEVER-1 may be useful prognostic and predictive markers in BC.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2017-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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