title: Identification of clinically relevant protein targets in prostate cancer with 2D-DIGE coupled mass spectrometry and systems biology network platform.
abstract: Prostate cancer (PCa) is the most common type of cancer found in men and among the leading causes of cancer death in the western world. In the present study, we compared the individual protein expression patterns from histologically characterized PCa and the surrounding benign tissue obtained by manual micro dissection using highly sensitive two-dimensional differential gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Proteomic data revealed 118 protein spots to be differentially expressed in cancer (n = 24) compared to benign (n = 21) prostate tissue. These spots were analysed by MALDI-TOF-MS/MS and 79 different proteins were identified. Using principal component analysis we could clearly separate tumor and normal tissue and two distinct tumor groups based on the protein expression pattern. By using a systems biology approach, we could map many of these proteins both into major pathways involved in PCa progression as well as into a group of potential diagnostic and/or prognostic markers. Due to complexity of the highly interconnected shortest pathway network, the functional sub networks revealed some of the potential candidate biomarker proteins for further validation. By using a systems biology approach, our study revealed novel proteins and molecular networks with altered expression in PCa. Further functional validation of individual proteins is ongoing and might provide new insights in PCa progression potentially leading to the design of novel diagnostic and therapeutic strategies.
authors.affiliation: Department of Oncology, Haematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumor Zentrum, University Hospital Eppendorf, Hamburg, Germany.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Ummanni
authors.forename: Frederike
authors.initials: F
authors.lastname: Mundt
authors.forename: Heike
authors.initials: H
authors.lastname: Pospisil
authors.forename: Simone
authors.initials: S
authors.lastname: Venz
authors.forename: Christian
authors.initials: C
authors.lastname: Scharf
authors.forename: Christine
authors.initials: C
authors.lastname: Barett
authors.forename: Maria
authors.initials: M
authors.lastname: Fälth
authors.forename: Jens
authors.initials: J
authors.lastname: Köllermann
authors.forename: Reinhard
authors.initials: R
authors.lastname: Walther
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Carsten
authors.initials: C
authors.lastname: Bokemeyer
authors.forename: Holger
authors.initials: H
authors.lastname: Sültmann
authors.forename: A
authors.initials: A
authors.lastname: Schuppert
authors.forename: Tim H
authors.initials: TH
authors.lastname: Brümmendorf
authors.forename: Stefan
authors.initials: S
authors.lastname: Balabanov
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D025341:Principal Component Analysis; D011467:Prostate / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D049490:Systems Biology / Q000379:methods*; D053719:Tandem Mass Spectrometry; D059467:Transcriptome; D057825:Two-Dimensional Difference Gel Electrophoresis
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins