Protein interactome of muscle invasive bladder cancer

PLoS One. 2015 Jan 8;10(1):e0116404. doi: 10.1371/journal.pone.0116404. eCollection 2015.

Abstract

Muscle invasive bladder carcinoma is a complex, multifactorial disease caused by disruptions and alterations of several molecular pathways that result in heterogeneous phenotypes and variable disease outcome. Combining this disparate knowledge may offer insights for deciphering relevant molecular processes regarding targeted therapeutic approaches guided by molecular signatures allowing improved phenotype profiling. The aim of the study is to characterize muscle invasive bladder carcinoma on a molecular level by incorporating scientific literature screening and signatures from omics profiling. Public domain omics signatures together with molecular features associated with muscle invasive bladder cancer were derived from literature mining to provide 286 unique protein-coding genes. These were integrated in a protein-interaction network to obtain a molecular functional map of the phenotype. This feature map educated on three novel disease-associated pathways with plausible involvement in bladder cancer, namely Regulation of actin cytoskeleton, Neurotrophin signalling pathway and Endocytosis. Systematic integration approaches allow to study the molecular context of individual features reported as associated with a clinical phenotype and could potentially help to improve the molecular mechanistic description of the disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Biomarkers, Tumor / metabolism
  • Databases, Factual
  • Endocytosis
  • Humans
  • Muscle Neoplasms / metabolism
  • Muscle Neoplasms / pathology*
  • Muscle Neoplasms / secondary
  • Nerve Growth Factors / metabolism
  • Phenotype
  • Protein Interaction Maps
  • Signal Transduction
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Nerve Growth Factors

Grants and funding

This work was supported by Marie Curie Actions — BCMolMed under grant agreement no. FP7-PEOPLE-2012-ITN-EID and the European Community’s Seventh Framework Programme under grant agreement no. 306157. Harald Mischak is the founder and co-owner of Mosaiques Diagnostics, who developed the CE-MS technology for clinical application. Akshay Bhat is an employee of Mosaiques Diagnostics. Bernd Mayer is the managing partner of emergentec biodevelopment GmbH, Austria. Paul Perco, Andreas Heinzel and Irmgard Mühlberger are employees of emergentec. Neither Mosaiques Diagnostics GmbH nor emergentec biodevelopment GmbH were involved in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The companies involved only provided financial support in the form of authors’ salaries and/or research materials. The specific roles of these authors are articulated in the ‘author contributions’ section.