Abstract A064: Mass spectrometry-based proteomics study makes apolipoprotein E a potential risk factor for prostate cancer

Abstract

Abstract 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 differential proteins only expressed in PCa samples. Of note, apolipoprotein E (APOE) was highly present 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 upregulation (fold change >1.5, P<0.05) comparing prostate adenocarcinoma vs. normal prostate gland. Accordingly, when extending the bioinformatics analysis to evaluate whole-exome and RNA-seq data using cBioportal, the most frequent genetic alteration found for APOE was amplification. RNA-seq data also confirmed a significant upregulation for APOE (P<0.05). We thus identify APOE as a key target in PCa, ascertaining it as a potential risk factor for this disease. Citation Format: Juan Bizzotto, Sofia Lage Vickers, Alejandra Paez, Carlos Scorticati, Javier Cotignola, Pia Valacco, Osvaldo Mazza, Elba Vazquez, Geraldine Gueron. Mass spectrometry-based proteomics study makes apolipoprotein E a potential risk factor for prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A064.