title: Novel robust biomarkers for human bladder cancer based on activation of intracellular signaling pathways.
abstract: We recently proposed a new bioinformatic algorithm called OncoFinder for quantifying the activation of intracellular signaling pathways. It was proved advantageous for minimizing errors of high-throughput gene expression analyses and showed strong potential for identifying new biomarkers. Here, for the first time, we applied OncoFinder for normal and cancerous tissues of the human bladder to identify biomarkers of bladder cancer. Using Illumina HT12v4 microarrays, we profiled gene expression in 17 cancer and seven non-cancerous bladder tissue samples. These experiments were done in two independent laboratories located in Russia and Canada. We calculated pathway activation strength values for the investigated transcriptomes and identified signaling pathways that were regulated differently in bladder cancer (BC) tissues compared with normal controls. We found, for both experimental datasets, 44 signaling pathways that serve as excellent new biomarkers of BC, supported by high area under the curve (AUC) values. We conclude that the OncoFinder approach is highly efficient in finding new biomarkers for cancer. These markers are mathematical functions involving multiple gene products, which distinguishes them from "traditional" expression biomarkers that only assess concentrations of single genes.
authors.affiliation: Pathway Pharmaceuticals, Wan Chai, Hong Kong, Hong Kong SAR. Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Ksenia
authors.initials: K
authors.lastname: Lezhnina
authors.affiliation: Department of Biological Sciences, University of Lethbridge, 4401 University Drive, Lethbridge, AB, T1K 3M4. Canada Cancer and Aging Research Laboratories, Lethbridge, AB, Canada.
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
authors.affiliation: Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Insilico Medicine, Inc, ETC, Johns Hopkins University, Baltimore, MD. Faculty of Biological and Medical Physics, Moscow Institute of Physics and Technology.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Zhavoronkov
authors.affiliation: Pathway Pharmaceuticals, Wan Chai, Hong Kong, Hong Kong SAR.
authors.forename: Mikhail B
authors.initials: MB
authors.lastname: Korzinkin
authors.affiliation: Group for Genomic Regulation of Cell Signaling Systems, Shemyakn-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
authors.forename: Anastasia A
authors.initials: AA
authors.lastname: Zabolotneva
authors.affiliation: P.A. Herzen Moscow Oncological Research Institute, Moscow, Russia.
authors.forename: Peter V
authors.initials: PV
authors.lastname: Shegay
authors.affiliation: Moscow 1st Oncological Hospital, Moscow, Russia.
authors.forename: Dmitry G
authors.initials: DG
authors.lastname: Sokov
authors.affiliation: Lomonosov Moscow State University, Faculty of Fundamental Medicine, Moscow, Russia. Russian medical postgraduate academy,Moscow, Russia.
authors.forename: Nurshat M
authors.initials: NM
authors.lastname: Gaifullin
authors.affiliation: P.A. Herzen Moscow Oncological Research Institute, Moscow, Russia.
authors.forename: Igor G
authors.initials: IG
authors.lastname: Rusakov
authors.affiliation: Pathway Pharmaceuticals, Wan Chai, Hong Kong, Hong Kong SAR. Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Aliper
authors.affiliation: Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Roumiantsev
authors.affiliation: P.A. Herzen Moscow Oncological Research Institute, Moscow, Russia.
authors.forename: Boris Y
authors.initials: BY
authors.lastname: Alekseev
authors.affiliation: Laboratory of Systems Biology, A.I. Burnasyan Federal Medical Biophysical Center, Moscow, Russia.
authors.forename: Nikolay M
authors.initials: NM
authors.lastname: Borisov
authors.affiliation: Pathway Pharmaceuticals, Wan Chai, Hong Kong, Hong Kong SAR. Laboratory of Bioinformatics, D. Rogachyov Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia. Group for Genomic Regulation of Cell Signaling Systems, Shemyakn-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
authors.forename: Anton A
authors.initials: AA
authors.lastname: Buzdin
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics*; D019295:Computational Biology / Q000379:methods*; D015870:Gene Expression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015398:Signal Transduction / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*; D001743:Urinary Bladder / Q000166:cytology; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor