title: Large-Scale SRM Screen of Urothelial Bladder Cancer Candidate Biomarkers in Urine.
abstract: Urothelial bladder cancer is a condition associated with high recurrence and substantial morbidity and mortality. Noninvasive urinary tests that would detect bladder cancer and tumor recurrence are required to significantly improve patient care. Over the past decade, numerous bladder cancer candidate biomarkers have been identified in the context of extensive proteomics or transcriptomics studies. To translate these findings in clinically useful biomarkers, the systematic evaluation of these candidates remains the bottleneck. Such evaluation involves large-scale quantitative LC-SRM (liquid chromatography-selected reaction monitoring) measurements, targeting hundreds of signature peptides by monitoring thousands of transitions in a single analysis. The design of highly multiplexed SRM analyses is driven by several factors: throughput, robustness, selectivity and sensitivity. Because of the complexity of the samples to be analyzed, some measurements (transitions) can be interfered by coeluting isobaric species resulting in biased or inconsistent estimated peptide/protein levels. Thus the assessment of the quality of SRM data is critical to allow flagging these inconsistent data. We describe an efficient and robust method to process large SRM data sets, including the processing of the raw data, the detection of low-quality measurements, the normalization of the signals for each protein, and the estimation of protein levels. Using this methodology, a variety of proteins previously associated with bladder cancer have been assessed through the analysis of urine samples from a large cohort of cancer patients and corresponding controls in an effort to establish a priority list of most promising candidates to guide subsequent clinical validation studies.
authors.affiliation: Genomics and Proteomics Research Unit, Department of Oncology, Luxembourg Institute of Health , 1 A-B rue Thomas Edison, L-1445 Strassen, Luxembourg.
authors.forename: Elodie
authors.identifier: 0000-0001-8780-3479
authors.initials: E
authors.lastname: Duriez
authors.affiliation: Univ. Grenoble Alpes , BIG-BGE, F-38000 Grenoble, France.|CEA , BIG-BGE, F-38000 Grenoble, France.|INSERM , BGE, F-38000 Grenoble, France.
authors.forename: Christophe D
authors.identifier: 0000-0003-0117-2480
authors.initials: CD
authors.lastname: Masselon
authors.affiliation: Genomics and Proteomics Research Unit, Department of Oncology, Luxembourg Institute of Health , 1 A-B rue Thomas Edison, L-1445 Strassen, Luxembourg.
authors.forename: Cédric
authors.identifier: 0000-0002-3742-5809
authors.initials: C
authors.lastname: Mesmin
authors.affiliation: Univ. Grenoble Alpes , BIG-BGE, F-38000 Grenoble, France.|CEA , BIG-BGE, F-38000 Grenoble, France.|INSERM , BGE, F-38000 Grenoble, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Court
authors.affiliation: NorLux Neuro-Oncology Laboratory, Department of Oncology, Luxembourg Institute of Health (LIH) , Luxembourg L-1526, Luxembourg.
authors.forename: Kevin
authors.initials: K
authors.lastname: Demeure
authors.affiliation: INSERM , U955 Eq07, Créteil 94000, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allory
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO) , Madrid 28029, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Malats
authors.affiliation: Department of Biology, Institute of Molecular Systems Biology, ETHZ , Zürich 8093, Switzerland.
authors.forename: Mariette
authors.initials: M
authors.lastname: Matondo
authors.affiliation: Institut Curie , Centre de Recherche, Paris 75005, France.|CNRS, UMR144, Equipe Oncologie Moléculaire , Paris 75248, France.
authors.forename: François
authors.initials: F
authors.lastname: Radvanyi
authors.affiliation: Univ. Grenoble Alpes , BIG-BGE, F-38000 Grenoble, France.|CEA , BIG-BGE, F-38000 Grenoble, France.|INSERM , BGE, F-38000 Grenoble, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Garin
authors.affiliation: Genomics and Proteomics Research Unit, Department of Oncology, Luxembourg Institute of Health , 1 A-B rue Thomas Edison, L-1445 Strassen, Luxembourg.
authors.forename: Bruno
authors.initials: B
authors.lastname: Domon
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine*; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000473:pathology / Q000652:urine*; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D040901:Proteomics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor
keywords: bladder cancer; candidate biomarkers; large-scale SRM screen; mass spectrometry; noninvasive; targeted proteomics; urine