title: Proteomics analysis of malignant and benign prostate tissue by 2D DIGE/MS reveals new insights into proteins involved in prostate cancer.
abstract: BACKGROUND
  The key to a more effective diagnosis, prognosis, and therapeutic management of prostate cancer (PCa) could lie in the direct analysis of cancer tissue. In this study, by comparative proteomics analysis of PCa and benign prostate hyperplasia (BPH) tissues we attempted to elucidate the proteins and regulatory pathways involved in this disease.
  
  
  METHODS
  The samples used in this study were fresh surgical tissues with clinically and histologically confirmed PCa (n = 19) and BPH (n = 33). We used two dimensional difference in gel electrophoresis (2D DIGE) coupled with mass spectrometry (MS) and bioinformatics analysis.
  
  
  RESULTS
  Thirty-nine spots with statistically significant 1.8-fold variation or more in abundance, corresponding to 28 proteins were identified. The IPA analysis pointed out to 3 possible networks regulated within MAPK, ERK, TGFB1, and ubiquitin pathways. Thirteen of the identified proteins, namely, constituents of the intermediate filaments (KRT8, KRT18, DES), potential tumor suppressors (ARHGAP1, AZGP1, GSTM2, and MFAP4), transport and membrane organization proteins (FABP5, GC, and EHD2), chaperons (FKBP4 and HSPD1) and known cancer marker (NME1) have been associated with prostate and other cancers by numerous proteomics, genomics or functional studies. We evidenced for the first time the dysregulation of 9 proteins (CSNK1A1, ARID5B, LYPLA1, PSMB6, RABEP1, TALDO1, UBE2N, PPP1CB, and SERPINB1) that may have role in PCa. The UBE2N, PSMB6, and PPP1CB, involved in cell cycle regulation and progression were evaluated by Western blot analysis which confirmed significantly higher abundances of UBE2N and PSMB6 and significantly lower abundance of PPP1CB in PCa.
  
  
  CONCLUSIONS
  In addition to the identification of substantial number of proteins with known association with PCa, the proteomic approach in this study revealed proteins not previously clearly related to PCa, providing a starting point for further elucidation of their function in disease initiation and progression.
authors.affiliation: Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Davalieva
authors.affiliation: Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia.
authors.forename: Ivana Maleva
authors.initials: IM
authors.lastname: Kostovska
authors.affiliation: Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Kiprijanovska
authors.affiliation: Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia.
authors.forename: Katerina
authors.initials: K
authors.lastname: Markoska
authors.affiliation: Labaratory for Histopathology, Clinical Hospital "Sistina", Skopje, Republic of Macedonia.
authors.forename: Katerina
authors.initials: K
authors.lastname: Kubelka-Sabit
authors.affiliation: Labaratory for Histopathology, Clinical Hospital "Sistina", Skopje, Republic of Macedonia.
authors.forename: Vanja
authors.initials: V
authors.lastname: Filipovski
authors.affiliation: University Clinic for Urology, University Clinical Centre "Mother Theresa", Skopje, Republic of Macedonia.
authors.forename: Sotir
authors.initials: S
authors.lastname: Stavridis
authors.affiliation: University Clinic for Urology, University Clinical Centre "Mother Theresa", Skopje, Republic of Macedonia.
authors.forename: Oliver
authors.initials: O
authors.lastname: Stankov
authors.affiliation: Institute of Pathology, Medical Faculty, University "St. Cyril and Methodius", Skopje, Republic of Macedonia.
authors.forename: Selim
authors.initials: S
authors.lastname: Komina
authors.affiliation: Institute of Pathology, Medical Faculty, University "St. Cyril and Methodius", Skopje, Republic of Macedonia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Petrusevska
authors.affiliation: Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia.
authors.forename: Momir
authors.initials: M
authors.lastname: Polenakovic
mesh_terms: D053263:Gene Regulatory Networks / Q000235:genetics*; D006801:Humans; D008297:Male; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D040901:Proteomics / Q000379:methods*; D057825:Two-Dimensional Difference Gel Electrophoresis / Q000379:methods*
keywords: 2D DIGE; MALDI MS; benign prostate hyperplasia; cancer biomarkers; prostate cancer