• Bladder cancer
• biosensor technologies
• fluid biopsy
• nanomaterials
• tumor treatment

• Biomarker
• Bladder cancer
• Early diagnosis
• Recurrence monitoring

• Humans
• Biomarkers, Tumor/genetics
• Urinary Bladder Neoplasms/diagnosis
• Urinary Bladder Neoplasms/surgery
• Cystoscopy/methods
• Risk Factors
• Early Diagnosis

Background: The Oncuria™ urine test for the detection of bladder cancer measures a multiplex protein signature. In this study, we investigated the influence of urinary cellularity, protein, and hematuria on the performance of the Oncuria™ test in an ex vivo experimental model. Materials and Methods: Pooled urine from healthy subjects was spiked with cultured benign (UROtsa) or malignant cells (T24), cellular proteins, or whole blood. The resulting samples were analyzed using the Oncuria™ test following the manufacturer’s instructions. Results: Urine samples obtained from healthy subjects were negative for bladder cancer by Oncuria™ test criteria. The majority of the manipulated conditions did not result in a false-positive test. The addition of whole blood (high concentration) did result in a false-positive result, but this was abrogated by sample centrifugation prior to analysis. The addition of cellular proteins (high concentration) resulted in a positive Oncuria™ test, and this was unaffected by pre-analysis sample centrifugation. Conclusions: The Oncuria™ multiplex test performed well in the ex vivo experimental model and shows promise for clinical application. The identification of patients who require additional clinical evaluation could reduce the need to subject patients who do not have bladder cancer to frequent, uncomfortable and expensive cystoscopic examinations, thus benefiting both patients and the healthcare system.

• biomarkers
• bladder cancer
• multiplex
• protein
• urinalysis

• Biomarkers
• Cancer
• Exosomes
• Extracellular vesicles
• Omics
• Urine

The development of accurate, non-invasive urinary assays for bladder cancer would greatly facilitate the detection and management of a disease that has a high rate of recurrence and progression. In this study, we employed a discovery and validation strategy to identify microRNA signatures that can perform as a non-invasive bladder cancer diagnostic assay. Expression profiling of 754 human microRNAs (TaqMan low density arrays) was performed on naturally voided urine samples from a cohort of 85 subjects of known bladder disease status (27 with active BCa). A panel of 46 microRNAs significantly associated with bladder cancer were subsequently monitored in an independent cohort of 121 subjects (61 with active BCa) using quantitative real-time PCR (RT-PCR). Multivariable modeling identified a 25-target diagnostic signature that predicted the presence of BCa with an estimated sensitivity of 87% at a specificity of 100% (AUC 0.982). With additional validation, the monitoring of a urinary microRNA biomarker panel could facilitate the non-invasive evaluation of patients under investigation for BCa.

• bladder cancer
• diagnostic biomarkers
• microRNA
• multiplex
• urinalysis

The early detection of bladder cancer is important as the disease has a high rate of recurrence and progression. The development of accurate, non-invasive urinary assays would greatly facilitate detection. In previous studies, we have reported the discovery and initial validation of mRNA biomarkers that may be applicable in this context. In this study, we evaluated the diagnostic performance of proposed molecular signatures in an independent cohort.

Forty-four mRNA transcripts were monitored blindly in urine samples obtained from a cohort of 196 subjects with known bladder disease status (89 with active BCa) using quantitative real-time PCR (RT-PCR). Statistical analyses defined associations of individual biomarkers with clinical data and the performance of predictive multivariate models was assessed using ROC curves. The majority of the candidate mRNA targets were confirmed as being associated with the presence of BCa over other clinical variables. Multivariate models identified an optimal 18-gene diagnostic signature that predicted the presence of BCa with a sensitivity of 85% and a specificity of 88% (AUC 0.935). Analysis of mRNA signatures in naturally micturated urine samples can provide valuable information for the evaluation of patients under investigation for BCa. Additional refinement and validation of promising multi-target signatures will support the development of accurate assays for the non-invasive detection and monitoring of BCa.

• bladder cancer
• diagnostic biomarkers
• multiplex
• non-invasive
• urinalysis

Despite advances in the surgical and medical treatment of bladder cancer, there have only been minor improvements in mortality and morbidity rates over the past decades. Urine-based markers help to improve diagnosing bladder cancer with the aim of complementing or probably in future replacing cystoscopy. Biomarkers may allow individualized risk stratification and support decision-making regarding therapy and follow-up. This review summarizes the existing urine-based biomarkers in bladder cancer. We conducted a comprehensive review of the literature. We conducted a PubMed/Medline based research on English language articles and selected original articles and review articles that provided both description and assessment of urinary markers at time of screening, initial diagnosis, monitoring and prognostic evaluation of urothelial bladder cancer. Our research covered studies published between 2000 and 2017. The aim of this study was to give clinicians keys to understand the existing or promising urinary markers that may become alternatives to cytology/cystoscopy pair in the near future. Many urinary markers are now available, often with superior sensitivity to cytology. Their uses have been evaluated in numerous clinical situations in addition to the time of initial diagnosis and surveillance such as cases of isolated macroscopic hematuria or atypical cytology discordant with the rest of the explorations. However, their superiority over the cytology/cystoscopy association is not demonstrated. These new markers are lacking for the most part of standardization and simplicity making their use in common practice difficult. the types and forms of these new markers are very heterogeneous among themselves and between the studies that evaluate them. Well-designed protocols and prospective, controlled trials are needed to provide the basis to determine whether integration of urine- and blood-based biomarkers into clinical decision-making will be of value for bladder cancer detection and screening in the future.

• Urothelial carcinoma
• bladder cancer
• detection
• outcomes
• screening
• surveillance
• urine biomarker

• biomarker
• chemokine CXCL16
• tumour biology
• urine
• urothelial cancer

Sequence alterations of the mitochondrial DNA (mtDNA) have been identified in many tu-mor types. Their nature is not entirely clear. Somatic mutation or shifts of heteroplasmic mtDNA vari-ants may play a role. These sequence alterations exhibit a sufficient frequency in all tumor types investi-gated thus far to justify their use as a tumor marker. This statement is supported by the high copy num-ber of mtDNA, which facilitates the detection of aberrant tumor-derived DNA in bodily fluids. This will be of special interest in tumors, which release a relatively high number of cells into bodily fluids, which are easily accessible, most strikingly in urinary bladder carcinoma. Due to the wide distribution of the observed base substitutions, deletions or insertions within the mitochondrial genome, high efforts for whole mtDNA sequencing (16.5 kb) from bodily fluids would be required, if the method would be in-tended for initial tumor screening. However, the usage of mtDNA for sensitive surveillance of known tumor diseases is a meaningful option, which may allow an improved non-invasive follow-up for the urinary bladder carcinoma, as compared to the currently existing cytological or molecular methods. Fol-lowing a short general introduction into mtDNA, this review demonstrates that the scenario of a sensi-tive cancer follow-up by mtDNA-analysis deserves more attention. It would be most important to inves-tigate precisely in the most relevant tumor types, if sequencing approaches in combination with simple PCR-assays for deletions/insertions in homopolymeric tracts has sufficient sensitivity to find most tu-mor-derived mtDNAs in bodily fluids.

• Bladder cancer
• Cancer risk
• Cancer surveillance
• Heteroplasmy
• MitoChip
• NGS
• mtDNA

• Bladder cancer
• endocan
• serum
• urine

• Bladder cancer
• biomarker
• protein
• urine

• 15958 Cancer Research UK

The search continues for optimal markers that can be utilized to improve bladder cancer detection and to predict disease recurrence. Although no single marker has yet replaced the need to perform cystoscopy and urine cytology, many tests have been evaluated and are being developed. In the future, these promising markers may be incorporated into standard practice to address the challenge of screening in addition to long-term surveillance of patients who have or are at risk for developing bladder cancer.

• Biomarkers
• bladder cancer
• transitional cell carcinoma
• urothelial carcinoma

Bladder cancer is one of the most prevalent cancers worldwide, but the treatment and management of this disease can be very successful if the disease is detected early. The development of molecular assays that could diagnose bladder cancer accurately, and at an early stage, would be a significant advance. Ideally, such molecular assays would be applicable to non-invasively obtained body fluids, and be designed not only for diagnosis but also for monitoring disease recurrence and response to treatment. In this article, we assess the performance of current diagnostic assays for bladder cancer and discuss some of the emerging biomarkers that could be developed to augment current bladder cancer detection strategies.

• Biomarker
• Bladder cancer
• Detection
• Molecular marker
• Surveillance
• Urine
• Urothelial carcinoma

• Biomarkers, Tumor/urine
• Carcinoma, Transitional Cell/urine
• Early Detection of Cancer/methods
• Humans
• Sensitivity and Specificity
• Urinary Bladder Neoplasms/urine

Current urine-based assays for bladder cancer (BCa) diagnosis lack accuracy, so the search for improved biomarkers continues. Through genomic and proteomic profiling of urine, we have identified a panel of biomarkers associated with the presence of BCa. In this study, we evaluated the utility of three of these biomarkers, interleukin 8 (IL-8), Matrix metallopeptidase 9 (MMP-9) and Syndecan in the diagnosis of BCa through urinalysis.

Voided urines from 127 subjects, cancer subjects (n = 64), non-cancer subjects (n = 63) were analyzed. The protein concentrations of IL-8, MMP-9, and Syndecan were assessed by enzyme-linked immunosorbent assay (ELISA). Data were also compared to a commercial ELISA-based BCa detection assay (BTA-Trak©) and urinary cytology. We used the area under the curve of a receiver operating characteristic (AUROC) to compare the performance of each biomarker.

Urinary protein concentrations of IL-8, MMP-9 and BTA were significantly elevated in BCa subjects. Of the experimental markers compared to BTA-Trak©, IL-8 was the most prominent marker (AUC; 0.79; 95% confidence interval [CI], 0.72-0.86). Multivariate regression analysis revealed that only IL-8 (OR; 1.51; 95% CI, 1.16-1.97, p = 0.002) was an independent factor for the detection of BCa.

These results suggest that the measurement of IL-8 in voided urinary samples may have utility for urine-based detection of BCa. These findings need to be confirmed in a larger, prospective cohort.

• proteinchip profiling
• proteomics
• tumor biomarker
• surface–enhanced laser desorption/ionization time-of-flight mass spectrometry (seldi-tof ms)

• Animals
• Computational Biology
• Humans
• Lasers
• Mass Spectrometry/methods
• Protein Array Analysis/methods
• Proteomics
• Surface Properties

• Biomarkers, Tumor/analysis
• Humans
• Hyaluronan Receptors/urine
• Hyaluronic Acid/analysis
• Keratins/analysis
• Lewis X Antigen/analysis
• Nuclear Proteins/analysis
• Proteomics
• Telomerase/analysis
• Urinary Bladder Neoplasms/diagnosis
• Urinary Bladder Neoplasms/therapy

• Biomarkers, Tumor/analysis
• Humans
• Neoplasm Recurrence, Local/diagnosis
• Sensitivity and Specificity
• Urinary Bladder Neoplasms/diagnosis
• Urine/cytology

• R01 CA-72821-06A2 NCI NIH HHS

• Electrophoresis, Gel, Two-Dimensional
• Humans
• Image Processing, Computer-Assisted/methods
• Isoelectric Point
• Molecular Weight
• Neoplasm Proteins/analysis
• Neoplasms/diagnosis
• Neoplasms/metabolism
• Proteome/analysis
• Proteomics/methods
• Reproducibility of Results

AIM: To study the alteration of nuclear matrix proteins (NMPs) in gastric cancer.

METHODS: The NMPs extracted from 22 cases of gastric cancer and normal gastric tissues were investigated by SDS-PAGE technique and the data were analyzed using Genetools analysis software.

RESULTS: Compared with normal gastric tissue, the expression of 30 ku and 28 ku NMPs in gastric cancer decreased significantly (P = 0.002, P = 0.001, P < 0.05). No significant difference was found in the expression of the two NMPs between the various differentiated grades (P = 0.947, P = 0.356) and clinical stages of gastric cancer (P = 0.920, P = 0.243, P > 0.05).

CONCLUSION: The results suggested that the alteration of NMPs in gastric cancer occurred at the early stage of gastric cancer development.

• Cell Nucleus/metabolism
• Electrophoresis, Polyacrylamide Gel
• Gastric Mucosa/metabolism
• Humans
• Nuclear Matrix-Associated Proteins/metabolism
• Stomach Neoplasms/metabolism

• Diagnostic Techniques, Urological
• Humans
• Neoplasm Staging/methods
• Urinary Bladder Neoplasms/diagnosis