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Metabolomics in the prediction of recurrence and progression of non-muscle invasive bladder cancer

Funder: Swiss National Science Foundation

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Project Summary: Metabolomics in the prediction of recurrence and progression of non-muscle invasive bladder cancerBackground: Bladder cancer (BCa) is the 7th most common cancer in men and the 17th most common cancer in women and accounts for an estimated 38200 deaths in 2012 in the European Union. Because of long-term survival and invasive follow-up, BCa is the most expensive of all cancers on a cost-per-case basis. At diagnosis, around 70% to 80% of patients have cancers confined to the epithelium or subepithelial tissue called non-muscle invasive BCa (NMIBC). These cases are usually treated with endoscopic surgery and intravesical therapy if needed. However, recurrence and progression are seen in up to 78% and 45% of the cases, respectively. Once progression into muscle-invasive disease develops, the surgical removal of the bladder needs to be performed. Because of its relapsing and progressing nature, surveillance of BCa consisting of cystoscopy and cytology is indicated. Because of the high cost and the invasiveness associated with BCa-surveillance, markers predicting recurrence and progression of BCa are urgently needed. One method to detect such markers is the analysis of metabolomics in urine. Recently, a BCa-specific signature of 35 metabolites in urine could be shown which was able to discriminate urine from healthy and BCa-patients as well as muscle-invasive from non-muscle-invasive disease. Aims: The aim of our study is the identification of a BCa-associated metabolic urine signature suggestive of recurrence and progression of NMIBC and the determination of the effect of intravesical therapy on the recurrence and progression signature. Material and Methods: Urine sediments and tissues from BCa patients collected at diagnosis and at various time-points after transurethral surgery or intravesical treatment will be analyzed. In total, samples of 600 patients are available for analysis. In a first step, the 35 metabolites detected previously will be evaluated for concordance in 80 BCa tissues. The verified metabolites will then further be verified on urine samples matched for recurrence and progression. Furthermore, the effect of intravesical therapy on the BCa-associated metabolic signature will be determined. Metabolites will be analyzed by liquid chromatography-couples mass spectrometry and identified using a metabolomic library containing data on 1000 metabolites. The statistical analysis will be performed with non-linear methods that examine interacting components within the data and will be verified to define a subset of metabolites that distinguish recurrent from non-recurrent and progressive from non-progressive disease. Relevance of the Project: The frequency, relapsing nature, and the invasive follow-up of patients with cystoscopy and cytology make BCa the most expensive of all cancers on a cost-per-case basis. This enormous health economic burden stimulated the search for non-invasive biomarkers. However, current evidence suggests that single biomarkers may be insufficient for effective monitoring and patient management. We aim to overcome the limitations of available biomarkers, and strive to characterize metabolic markers in urine for the prediction of BCa recurrence, progression and BCa-surveillance. The development of non-invasive metabolic markers for the diagnosis and surveillance of BCa-patients has broad implications for the improvement of the clinical management of BCa.
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    1103 Clinical Sciences


    1112 Oncology and Carcinogenesis

  • RCDC


  • RCDC

    Clinical Research

  • RCDC

    Urologic Diseases




    2.1 Biological and endogenous factors


    4.1 Discovery and preclinical testing of markers and technologies

  • Health Research Areas


  • Broad Research Areas

    Clinical Medicine and Science