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      Bladder Cancer Detection and Monitoring: Assessment of Urine- and Blood-Based Marker Tests

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          Abstract

          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.

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          Bladder cancer.

          Donald S Kaufman, William U Shipley, Adam S. Feldman (2009)
          Bladder cancer is a heterogeneous disease, with 70% of patients presenting with superficial tumours, which tend to recur but are generally not life threatening, and 30% presenting as muscle-invasive disease associated with a high risk of death from distant metastases. The main presenting symptom of all bladder cancers is painless haematuria, and the diagnosis is established by urinary cytology and transurethral tumour resection. Intravesical treatment is used for carcinoma in situ and other high grade non-muscle-invasive tumours. The standard of care for muscle-invasive disease is radical cystoprostatectomy, and several types of urinary diversions are offered to patients, with quality of life as an important consideration. Bladder preservation with transurethral tumour resection, radiation, and chemotherapy can in some cases be equally curative. Several chemotherapeutic agents have proven to be useful as neoadjuvant or adjuvant treatment and in patients with metastatic disease. We discuss bladder preserving approaches, combination chemotherapy including new agents, targeted therapies, and advances in molecular biology.
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            Defining molecular profiles of poor outcome in patients with invasive bladder cancer using oligonucleotide microarrays.

            Marta Sánchez-Carbayo, Nicholas D. Socci, Juanjo Lozano … (2006)
            Bladder cancer is a common malignancy characterized by a poor clinical outcome when tumors progress into invasive disease. We sought to define genetic signatures characteristic of aggressive clinical behavior in advanced bladder tumors. Oligonucleotide arrays were utilized to analyze the transcript profiles of 105 bladder tumors: 33 superficial, 72 invasive lesions, and 52 normal urothelium. Hierarchical clustering and supervised algorithms were used to classify and stratify bladder tumors on the basis of stage, node metastases, and overall survival. Immunohistochemical analyses on bladder cancer tissue arrays (n = 294 cases) served to validate associations between marker expression, staging and outcome. Hierarchical clustering classified normal urothelium, superficial, and invasive tumors with 82.2% accuracy, and stratified bladder tumors on the basis of clinical outcome. Predictive algorithms rendered an 89%-correct rate for tumor staging using genes differentially expressed between superficial and invasive tumors. Accuracies of 82% and 90% were obtained for predicting overall survival when considering all patients with bladder cancer or only patients with invasive disease, respectively. A genetic profile consisting of 174 probes was identified in those patients with positive lymph nodes and poor survival. Two independent Global Test runs confirmed the robust association of this profile with lymph node metastases (P = 7.3(-13)) and overall survival (P = 1.9(-14)) simultaneously. Immunohistochemical analyses on tissue arrays sustained the significant association of synuclein with tumor staging and clinical outcome (P = .002). Gene profiling provides a genomic-based classification scheme of diagnostic and prognostic utility for stratifying advanced bladder cancer. Identification of this poor outcome profile could assist in selecting patients who may benefit from more aggressive therapeutic intervention.
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              Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro.

              Jørgen Kjems, Jesper Bramsen, Michael Borre … (2009)
              microRNAs (miRNA) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Here, we profiled the expression of 290 unique human miRNAs in 11 normal and 106 bladder tumor samples using spotted locked nucleic acid-based oligonucleotide microarrays. We identified several differentially expressed miRNAs between normal urothelium and cancer and between the different disease stages. miR-145 was found to be the most down-regulated in cancer compared with normal, and miR-21 was the most up-regulated in cancer. Furthermore, we identified miRNAs that significantly correlated to the presence of concomitant carcinoma in situ. We identified several miRNAs with prognostic potential for predicting disease progression (e.g., miR-129, miR-133b, and miR-518c*). We localized the expression of miR-145, miR-21, and miR-129 to urothelium by in situ hybridization. We then focused on miR-129 that exerted significant growth inhibition and induced cell death upon transfection with a miR-129 precursor in bladder carcinoma cell lines T24 and SW780 cells. Microarray analysis of T24 cells after transfection showed significant miR-129 target down-regulation (P = 0.0002) and pathway analysis indicated that targets were involved in cell death processes. By analyzing gene expression data from clinical tumor samples, we identified significant expression changes of target mRNA molecules related to the miRNA expression. Using luciferase assays, we documented a direct link between miR-129 and the two putative targets GALNT1 and SOX4. The findings reported here indicate that several miRNAs are differentially regulated in bladder cancer and may form a basis for clinical development of new biomarkers for bladder cancer.
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                Author and article information

                Contributors
                Steve Goodison: +1-407-2667401 , +1-407-2667402 , steven.goodison@orlandohealth.com
                Journal
                Journal ID (nlm-ta): Mol Diagn Ther
                Journal ID (iso-abbrev): Mol Diagn Ther
                Title: Molecular Diagnosis & Therapy
                Publisher: Springer International Publishing AG (Cham )
                ISSN (Print): 1177-1062
                ISSN (Electronic): 1179-2000
                Publication date (Electronic): 12 March 2013
                Publication date PMC-release: 12 March 2013
                Publication date (Print): April 2013
                Volume: 17
                Issue: 2
                Pages: 71-84
                Affiliations
                Cancer Research Institute, MD Anderson Cancer Center Orlando, 6900 Lake Nona Blvd, Orlando, FL 32827 USA
                Article
                Publisher ID: 23
                DOI: 10.1007/s40291-013-0023-x
                PMC ID: 3627848
                PubMed ID: 23479428
                SO-VID: db4a9191-cbcf-4e32-abee-a6d4b764bf8a
                Copyright © © The Author(s) 2013
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

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                Categories
                Subject: Review Article
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                issue-copyright-statement © Springer International Publishing Switzerland 2013

                ScienceOpen disciplines: Molecular medicine
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                ScienceOpen disciplines: Molecular medicine

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