INVESTIGADORES
VAZQUEZ Elba Susana
congresos y reuniones científicas
Título:
Integrative prostate cancer tissue proteomics dissects clear and distinct proteomes for human prostate cancer and benign prostatic hyperplasia
Autor/es:
VAZQUEZ, ELBA; LAGE VICKERS, SOFIA; PAEZ ALEJANDRA; BIZZOTO, JUAN; GUERON GUERALDINE; NAVONE, NORA; VALACCO, PIA
Lugar:
Orlando
Reunión:
Congreso; Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017
Institución organizadora:
AACR
Resumen:
Integrative prostate cancer tissue proteomics dissects clear and distinct proteomes for human prostate cancer and benign prostatic hyperplasiaCurrent approaches in proteomics techniques and MS systems have revived the quest for novel biomarkers in prostate cancer (PCa) boosting the molecular characterization of the disease. To reveal fundamental differences between benign and malignant growth of prostate cells we combined a new protein extraction procedure that disrupts the crosslinked proteins from the previously formaldehyde-fixed paraffin-embedded tissue samples with in depth proteomic analysis (ESI-MS/MS). Human PCa and benign prostatic hyperplasia (BPH) tissue samples were obtained using phase-transfer surfactant-aided extraction/tryptic digestion of formalin-fixed and paraffin-embedded sections mounted on microscope slides. Data analysis was based on label-free spectral counting, identifying with a minimum of two peptides, 1331 and 1239 proteins in PCa and BPH tissue proteomes respectively. 71 proteins were exclusively present in PCa samples, while 122 proteins where exclusively present in BPH samples. In order to prioritize candidate markers for PCa, we compared protein expression based on normalized spectral counts between tissue samples. We set as cut-offs proteins that were found with a minimum of three peptides within the PCa and BPH proteomes. This filter resulted in the selection of two clusters of 11 and 16 proteins respectively. The data sets highlighted distinct proteins that were previously studied in the context of prostate cancer progression, including SSBP1, GDF15, NDRG1, C4A & APOE for PCa and DUSP3, MME, SRI, DSG1 for BPH, thus providing further confirmation for the robustness of our quantification method. We next subjected our candidate list to bioinformatics analysis (Oncomine). Accordingly, the 5 proteins aforementioned for PCa were significantly up-regulated (fold change >1.5, P0.05) in prostate adenocarcinoma vs. normal prostate gland. Whole exome analysis (cBioportal), revealed amplification as the most frequent genetic alteration and RNASeq data also confirmed a significant up-regulation for these proteins (P0.05). Strikingly, proteins associated with BPH were significantly down-regulated (fold change >1.5, P0.05) across the same comparison and RNASeq data also confirmed a significant down-regulation for these proteins (P0.05). This report showcases significant and extensive differences in protein expression patterns between BPH and prostate carcinoma. Proteome analysis of prostate tissues should help to disclose the molecular mechanisms underlying prostate malignant growth, resulting in new sets of biomarkers for diagnostic, prognostic, and therapeutic use.