A multiplex immunoassay for the non-invasive detection of bladder cancer

471 Background: Urine based assays that can non-invasively detect bladder cancer (BCa) have the potential to reduce unnecessary and invasive procedures. The purpose of this study was to develop a multiplex immunoassay that can accurately and simultaneously monitor 10 diagnostic urinary protein biomarkers for application as a non-invasive test for BCa detection Methods: A custom electrochemiluminescent (ECL) multiplex assay was constructed (Meso Scale Diagnostics, LLC, Rockville, MD) to detect the following urinary proteins; IL8, MMP9, MMP10, ANG, APOE, SDC1, A1AT, PAI1, CA9 and VEGFA. Voided urine samples from two cohorts (cohort #1 n = 62 and cohort #2 n = 200) were collected prior to cystoscopy and samples were analyzed blinded to the clinical status of the participants. Means (±SD) and receiver operating characteristic (ROC) curve analysis were used to compare assay performance and to assess the diagnostic accuracy of the diagnostic signature. Results: Comparative diagnostic performance analyses revealed an AUROC value of 0.9258 for the multiplex assay and 0.9467 for the combination of the single-target ELISA assays (p = 0.625), so there was no loss of diagnostic utility for the MSD multiplex assay. Analysis of the independent 200-sample cohort using the multiplex assay achieved an overall diagnostic sensitivity of 0.85, specificity of 0.81, positive predictive value 0.82 and negative predictive value 0.84. Conclusions: It is technically feasible to simultaneously monitor complex urinary diagnostic signatures in a single assay without loss of performance. The described protein-based assay has the potential to be developed for the non-invasive detection of BCa.

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Epigenomic and Metabolomic Integration Reveals Dynamic Metabolic Regulation in Bladder Cancer

Cancers ◽

10.3390/cancers13112719 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2719

Author(s):

Alba Loras ◽

Cristina Segovia ◽

José Luis Ruiz-Cerdá

Keyword(s):

Bladder Cancer ◽

Cancer Biology ◽

Metabolic Regulation ◽

Tumor Development ◽

Dna Methyltransferases ◽

Pentose Phosphate ◽

Metabolic Reprogramming ◽

Oncogenic Signaling ◽

Invasive Approach ◽

Non Invasive

Bladder cancer (BC) represents a clinical, social, and economic challenge due to tumor-intrinsic characteristics, limitations of diagnostic techniques and a lack of personalized treatments. In the last decade, the use of liquid biopsy has grown as a non-invasive approach to characterize tumors. Moreover, the emergence of omics has increased our knowledge of cancer biology and identified critical BC biomarkers. The rewiring between epigenetics and metabolism has been closely linked to tumor phenotype. Chromatin remodelers interact with each other to control gene silencing in BC, but also with stress-inducible factors or oncogenic signaling cascades to regulate metabolic reprogramming towards glycolysis, the pentose phosphate pathway, and lipogenesis. Concurrently, one-carbon metabolism supplies methyl groups to histone and DNA methyltransferases, leading to the hypermethylation and silencing of suppressor genes in BC. Conversely, α-KG and acetyl-CoA enhance the activity of histone demethylases and acetyl transferases, increasing gene expression, while succinate and fumarate have an inhibitory role. This review is the first to analyze the interplay between epigenome, metabolome and cell signaling pathways in BC, and shows how their regulation contributes to tumor development and progression. Moreover, it summarizes non-invasive biomarkers that could be applied in clinical practice to improve diagnosis, monitoring, prognosis and the therapeutic options in BC.

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A Case of Extravesical Metastases Occurring after Transurethral Resection of Non-Invasive Bladder Cancer

Journal of the Korean Society of Radiology ◽

10.3348/jksr.2018.78.2.141 ◽

2018 ◽

Vol 78 (2) ◽

pp. 141 ◽

Cited By ~ 1

Author(s):

Ga Ram Kang ◽

Dong Wan Sohn ◽

Dong Jin Chung

Keyword(s):

Bladder Cancer ◽

Transurethral Resection ◽

Invasive Bladder Cancer ◽

Non Invasive

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Re: Factors affecting recurrence and progression of high grade non invasive bladder cancer treated by intravesical BCG.

Pakistan Journal of Medical Sciences ◽

10.12669/pjms.306.6408 ◽

2014 ◽

Vol 30 (6) ◽

Author(s):

Haichao Huang ◽

Jie Jin ◽

Xin Li

Keyword(s):

Bladder Cancer ◽

Invasive Bladder Cancer ◽

High Grade ◽

Factors Affecting ◽

Non Invasive ◽

Intravesical Bcg

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Development of 3-Hydroxyanthranilic acid-based Integrated Non-invasive Biosensor for Bladder Cancer Detection

Urological Science ◽

10.1016/j.urols.2015.06.200 ◽

2015 ◽

Vol 26 (2) ◽

pp. S47-S48

Author(s):

Yuh-Shyan Tsai ◽

Yeong-Chin Jou ◽

Yen-Ping Tsai ◽

Bin-Da Liu ◽

Hung-In Lin ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Detection ◽

Non Invasive ◽

Hydroxyanthranilic Acid

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Diagnostic Performance of Oncuria™, a Urinalysis Test for Bladder Cancer

10.21203/rs.3.rs-253377/v1 ◽

2021 ◽

Author(s):

Yosuke Hirasawa ◽

Ian Pagano ◽

Runpu Chen ◽

Yijun Sun ◽

Yunfeng Dai ◽

...

Keyword(s):

Bladder Cancer ◽

Diagnostic Performance ◽

Clinical Laboratory ◽

Demographic Data ◽

Roc Curves ◽

Low Grade ◽

Linear Discriminant ◽

Non Invasive ◽

Diagnostic Panel ◽

Parallel Measurement

Abstract Background: Due to insufficient accuracy, urine-based assays currently have a limited role in the management of patients with bladder cancer. The identification of multiplex molecular signatures associated with disease has the potential to address this deficiency and to assist with accurate, non-invasive diagnosis and monitoring. Methods: To evaluate the performance of Oncuria™, a multiplex immunoassay for bladder detection in voided urine samples. The test was evaluated in a multi-institutional cohort of 362 prospectively collected subjects presenting for bladder cancer evaluation. The parallel measurement of 10 biomarkers (A1AT, APOE, ANG, CA9, IL8, MMP9, MMP10, PAI1, SDC1 and VEGFA) was performed in an independent clinical laboratory. The ability of the test to identify patients harboring bladder cancer was assessed. Bladder cancer status was confirmed by cystoscopy and tissue biopsy. The association of biomarkers and demographic factors was evaluated using linear discriminant analysis (LDA) and predictive models were derived using supervised learning and cross-validation analyses. Diagnostic performance was assessed using ROC curves.Results: The combination of the 10 biomarkers provided an AUROC 0.93 [95% CI: 0.87 – 0.98], outperforming any single biomarker. The addition of demographic data (age, sex, and race) into a hybrid signature improved the diagnostic performance AUROC 0.95 [95% CI: 0.90 – 1.00]. The hybrid signature achieved an overall sensitivity of 0.93, specificity of 0.93, PPV of 0.65 and NPV of 0.99 for bladder cancer classification. Sensitivity values of the diagnostic panel for high-grade bladder cancer, low-grade bladder cancer, MIBC and NMIBC were 0.94, 0.89, 0.97 and 0.93, respectively. Conclusions: Urinary levels of a biomarker panel enabled the accurate discrimination of bladder cancer patients and controls. The multiplex Oncuria™ test can achieve the efficient and accurate detection and monitoring of bladder cancer in a non-invasive patient setting.

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The pattern of urine cytology among patients with clinical diagnosis of bladder tumor in a tertiary hospital northwest Nigeria

International Surgery Journal ◽

10.18203/2349-2902.isj20194402 ◽

2019 ◽

Vol 6 (10) ◽

pp. 3521

Author(s):

Ahmed M. Umar ◽

Uzodimma E. Onwuasoanya ◽

Emmanuel U. Oyibo ◽

Adamu Dahiru ◽

Ismaila A. Mungadi

Keyword(s):

Bladder Cancer ◽

Clinical Diagnosis ◽

Bladder Tumour ◽

Tertiary Hospital ◽

Urine Cytology ◽

Female Ratio ◽

Non Invasive ◽

And Gender ◽

Low Sensitivity ◽

Age Range

Background: Urine cytology is a simple, safe, non-invasive and cheap investigation that is used as adjunct to cystoscopy in the diagnosis of bladder cancer. Its low sensitivity is a major limitation against its use as a sole diagnostic test for bladder cancer. The objective of this study was to determine the pattern of urine cytology seen in patients with clinical diagnosis of bladder tumour in our practice.Methods: This is a retrospective study of patients with clinical diagnosis of bladder tumour that had urine cytology in our centre. The age and gender of the patients, number of urine cytology per patient per year and cytologic diagnosis were analysed using the SPSS 20.Results: During the period under review, a total of 512 urine cytology was done for patients with clinical diagnosis of bladder tumour. The age range of the patients was 6 to 90 years with modal age of 60 years. 457 (89.3%) were males while 54 (10.5%) were females and 1 (0.2%) was unspecified. Male to female ratio was 8.5:1. The highest number of urine cytology was done in 2013 with 64 (12.5%) while the least number was 1 (0.2%) recorded in 2001 and 2003. Only 68 (13.3%) specimens were reported to be malignant while 245 (47.9%) were reported as negative representing the most common cytological diagnosis in the study.Conclusions: Although urine cytology is useful in the diagnostic workup of patients with bladder mass, it is unlikely it would supplant cystoscopy and biopsy in the diagnosis of bladder cancer.

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Non-invasive detection of bladder cancer through the analysis of driver gene mutations and aneuploidy

10.1101/203976 ◽

2017 ◽

Cited By ~ 3

Author(s):

Simeon Springer ◽

Maria Del Carmen Rodriguez Pena ◽

Lu Li ◽

Christopher Douville ◽

Yuxuan Wang ◽

...

Keyword(s):

At Risk ◽

Bladder Cancer ◽

Gene Mutations ◽

Urine Samples ◽

Driver Gene ◽

Low Grade ◽

Invasive Approach ◽

Non Invasive ◽

Patients At Risk ◽

Copy Number Changes

AbstractCurrent non-invasive approaches for bladder cancer (BC) detection are suboptimal. We report the development of non-invasive molecular test for BC using DNA recovered from cells shed into urine. This “UroSEEK” test incorporates assays for mutations in 11 genes and copy number changes on 39 chromosome arms. We first evaluated 570 urine samples from patients at risk for BC (microscopic hematuria or dysuria). UroSEEK was positive in 83% of patients that developed BC, but in only 7% of patients who did not develop BC. Combined with cytology, 95% of patients that developed BC were positive. We then evaluated 322 urine samples from patients soon after their BCs had been surgically resected. UroSEEK detected abnormalities in 66% of the urine samples from these patients, sometimes up to 4 years prior to clinical evidence of residual neoplasia, while cytology was positive in only 25% of such urine samples. The advantages of UroSEEK over cytology were particularly evident in low-grade tumors, wherein cytology detected none while UroSEEK detected 67% of 49 cases. These results establish the foundation for a new, non-invasive approach to the detection of BC in patients at risk for initial or recurrent disease.

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