title: Integrative analysis of extracellular and intracellular bladder cancer cell line proteome with transcriptome: improving coverage and validity of -omics findings.
abstract: Characterization of disease-associated proteins improves our understanding of disease pathophysiology. Obtaining a comprehensive coverage of the proteome is challenging, mainly due to limited statistical power and an inability to verify hundreds of putative biomarkers. In an effort to address these issues, we investigated the value of parallel analysis of compartment-specific proteomes with an assessment of findings by cross-strategy and cross-omics (proteomics-transcriptomics) agreement. The validity of the individual datasets and of a "verified" dataset based on cross-strategy/omics agreement was defined following their comparison with published literature. The proteomic analysis of the cell extract, Endoplasmic Reticulum/Golgi apparatus and conditioned medium of T24 vs. its metastatic subclone T24M bladder cancer cells allowed the identification of 253, 217 and 256 significant changes, respectively. Integration of these findings with transcriptomics resulted in 253 "verified" proteins based on the agreement of at least 2 strategies. This approach revealed findings of higher validity, as supported by a higher level of agreement in the literature data than those of individual datasets. As an example, the coverage and shortlisting of targets in the IL-8 signalling pathway are discussed. Collectively, an integrative analysis appears a safer way to evaluate -omics datasets and ultimately generate models from valid observations.
authors.affiliation: Biotechnology Division, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.|Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Latosinska
authors.affiliation: Biotechnology Division, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Manousos
authors.initials: M
authors.lastname: Makridakis
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Frantzi
authors.affiliation: GenomeScan B.V., Leiden, The Netherlands.|Institut National de la Santé et de la Recherche Médicale (INSERM), Institut of Cardiovascular and Metabolic Disease, Toulouse, France.|Université Toulouse III Paul-Sabatier, Toulouse, France.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Borràs
authors.affiliation: GenomeScan B.V., Leiden, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Janssen
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
authors.forename: William
authors.initials: W
authors.lastname: Mullen
authors.affiliation: Biotechnology Division, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Jerome
authors.initials: J
authors.lastname: Zoidakis
authors.affiliation: Department of Urology, University of Lübeck, Lübeck, Germany.|Department of Urology and Urological Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Axel S
authors.initials: AS
authors.lastname: Merseburger
authors.affiliation: RWTH-Aachen, Institute for Molecular Cardiovascular Research (IMCAR), Aachen, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Jankowski
authors.affiliation: Mosaiques Diagnostics GmbH, Hannover, Germany.|BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.affiliation: Biotechnology Division, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Vlahou
mesh_terms: D045744:Cell Line, Tumor; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D059467:Transcriptome / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016209:Interleukin-8; D009363:Neoplasm Proteins; D010455:Peptides; D020543:Proteome; D012333:RNA, Messenger