Proteomics analysis of malignant and benign prostate tissue by 2D DIGE/MS reveals new insights into proteins involved in prostate cancer
2015; Wiley; Volume: 75; Issue: 14 Linguagem: Inglês
10.1002/pros.23034
ISSN1097-0045
AutoresKatarina Davalieva, Ivana Maleva Kostovska, Sanja Kiprijanovska, Katerina Markoska, Katerina Kubelka‐Sabit, Vanja Filipovski, Сотир Ставридис, Оливер Станков, Selim Komina, Gordana Petruševska, Momir Polenaković,
Tópico(s)Ubiquitin and proteasome pathways
ResumoThe ProstateVolume 75, Issue 14 p. 1586-1600 Original Article Proteomics analysis of malignant and benign prostate tissue by 2D DIGE/MS reveals new insights into proteins involved in prostate cancer Katarina Davalieva, Corresponding Author Katarina Davalieva Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia Correspondence to: Katarina Davalieva, PhD, Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Krste Misirkov 2, 1000 Skopje, Republic of Macedonia. E-mail: [email protected]Search for more papers by this authorIvana Maleva Kostovska, Ivana Maleva Kostovska Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of MacedoniaSearch for more papers by this authorSanja Kiprijanovska, Sanja Kiprijanovska Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of MacedoniaSearch for more papers by this authorKaterina Markoska, Katerina Markoska Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of MacedoniaSearch for more papers by this authorKaterina Kubelka-Sabit, Katerina Kubelka-Sabit Labaratory for Histopathology, Clinical Hospital "Sistina", Skopje, Republic of MacedoniaSearch for more papers by this authorVanja Filipovski, Vanja Filipovski Labaratory for Histopathology, Clinical Hospital "Sistina", Skopje, Republic of MacedoniaSearch for more papers by this authorSotir Stavridis, Sotir Stavridis University Clinic for Urology, University Clinical Centre "Mother Theresa", Skopje, Republic of MacedoniaSearch for more papers by this authorOliver Stankov, Oliver Stankov University Clinic for Urology, University Clinical Centre "Mother Theresa", Skopje, Republic of MacedoniaSearch for more papers by this authorSelim Komina, Selim Komina Institute of Pathology, Medical Faculty, University "St. Cyril and Methodius", Skopje, Republic of MacedoniaSearch for more papers by this authorGordana Petrusevska, Gordana Petrusevska Institute of Pathology, Medical Faculty, University "St. Cyril and Methodius", Skopje, Republic of MacedoniaSearch for more papers by this authorMomir Polenakovic, Momir Polenakovic Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of MacedoniaSearch for more papers by this author Katarina Davalieva, Corresponding Author Katarina Davalieva Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of Macedonia Correspondence to: Katarina Davalieva, PhD, Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Krste Misirkov 2, 1000 Skopje, Republic of Macedonia. E-mail: [email protected]Search for more papers by this authorIvana Maleva Kostovska, Ivana Maleva Kostovska Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of MacedoniaSearch for more papers by this authorSanja Kiprijanovska, Sanja Kiprijanovska Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of MacedoniaSearch for more papers by this authorKaterina Markoska, Katerina Markoska Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of MacedoniaSearch for more papers by this authorKaterina Kubelka-Sabit, Katerina Kubelka-Sabit Labaratory for Histopathology, Clinical Hospital "Sistina", Skopje, Republic of MacedoniaSearch for more papers by this authorVanja Filipovski, Vanja Filipovski Labaratory for Histopathology, Clinical Hospital "Sistina", Skopje, Republic of MacedoniaSearch for more papers by this authorSotir Stavridis, Sotir Stavridis University Clinic for Urology, University Clinical Centre "Mother Theresa", Skopje, Republic of MacedoniaSearch for more papers by this authorOliver Stankov, Oliver Stankov University Clinic for Urology, University Clinical Centre "Mother Theresa", Skopje, Republic of MacedoniaSearch for more papers by this authorSelim Komina, Selim Komina Institute of Pathology, Medical Faculty, University "St. Cyril and Methodius", Skopje, Republic of MacedoniaSearch for more papers by this authorGordana Petrusevska, Gordana Petrusevska Institute of Pathology, Medical Faculty, University "St. Cyril and Methodius", Skopje, Republic of MacedoniaSearch for more papers by this authorMomir Polenakovic, Momir Polenakovic Research Centre for Genetic Engineering and Biotechnology "Georgi D Efremov", Macedonian Academy of Sciences and Arts, Skopje, Republic of MacedoniaSearch for more papers by this author First published: 12 June 2015 https://doi.org/10.1002/pros.23034Citations: 54 Conflict of interest: None Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat 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. CONCLUSION 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. Prostate 75:1586–1600, 2015. © 2015 Wiley Periodicals, Inc. Supporting Information Additional supporting information may be found in the online version of this article at the publisher's web-site. Filename Description pros23034-sup-0001-SuppData-S1.doc888 KB supporting information. pros23034-sup-0001-SuppTab-S1.doc101 KB Supporting Information Table S1: Clinical information of patients included in the study together with their PSA levels, histology grading and tumor stage. pros23034-sup-0001-SuppTab-S2.doc380.5 KB Supporting Information Table S2: Functional characterization and association with prostate and other types of malignancy of 13 proteins with differential abundance between PCa and BPH. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. REFERENCES 1 Nadler RB, Humphrey PA, Smith DS, Catalona WJ, Ratliff TL. Effect of inflammation and benign prostatic hyperplasia on elevated serum prostate specific antigen levels. 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