Mass Spectrometry-Based Proteomics Study Makes Apolipoprotein E a potential risk factor for prostate cancer

VAZQUEZ, ELBA; BIZZOTO, JUAN; LAGE VICKERS, SOFIA; PAEZ ALEJANDRA; SCORTICATI CARLOS; COTIGNOLA, JAVIER; VALACCO, PIA; MAZZA OSVALDO; GUERON GUERALDINE

Orlando

Congreso; Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017

AACR

Proteomics represents an important tool for the identification of new molecular targets for prostate cancer (PCa) tailored therapy. Innovative high-throughput proteomic platforms are now identifying and quantifying new specific and sensitive biomarkers for PCa detection, stratification and treatment. Formalin-fixed and paraffin-embedded (FF-PE) sections mounted on microscope slides are hard to achieve given the low peptide yield obtained from the slides. Here we performed an innovative protocol for an in-depth quantitative mass spectrometry-based proteomics analysis of FF-PE PCa and benign prostate hyperplasia (BPH) sections, using phase-transfer surfactant-aided extraction/tryptic digestion of FF-PE proteins. Results yielded a list of 50 proteins only present in PCa and absent in BPH samples. Of note Apolipoprotein E (APO E) was highly detected in carcinoma samples. Furthermore, to evaluate the clinical significance of APOE in PCa we performed a bioinformatics analysis using the Oncomine database. We identified 16 publicly available gene expression microarray datasets comparing prostate adenocarcinoma versus normal prostate, which met our eligibility criteria. We carried out meta-analysis combining the data from the independent datasets. APOE was ranked by its P-value for every analysis scoring a gene rank and then we obtained a median rank (Median P-value rank across datasets). APOE showed a significant up-regulation (fold change >1.5, P