Mass Spectrometry-Based proteomics study makes Apolipoprotein E a potential risk factor for prostate cancer

ANSELMINO NICOLAS; COTIGNOLA JAVIER; LAGE VICKERS SOFIA; VAZQUEZ ELBA S.; BIZZOTTO JUAN; VALACCO PIA; GUERON GERALDINE

Sao Paulo

Congreso; Second AACR International Conference. Translational Cancer Medicine; 2018

AACR

Proteomics represents an important tool for the identification of new moleculartargets for prostate cancer (PCa) tailored therapy. Innovative high-throughputproteomic platforms are now identifying and quantifying new specific and sensitivebiomarkers for PCa detection, stratification and treatment. Formalin-fixed andparaffin-embedded (FF-PE) sections mounted on microscope slides are hard toachieve given the low peptide yield obtained from the slides. Here we performedan innovative protocol for an in-depth quantitative mass spectrometry-basedproteomics analysis of FF-PE PCa and benign prostate hyperplasia (BPH) sections,using phase-transfer surfactant-aided extraction/tryptic digestion of FF-PEproteins. Results yielded a list of 50 differential proteins only expressed in PCasamples. Of note Apolipoprotein E (APO E) was highly present in carcinomasamples. Furthermore, to evaluate the clinical significance of APOE in PCa weperformed a bioinformatics analysis using the Oncomine database. We identified 16publicly available gene expression microarray datasets comparing prostateadenocarcinoma versus normal prostate, which met our eligibility criteria. Wecarried out meta-analysis combining the data from the independent datasets. APOEwas ranked by its P-value for every analysis scoring a gene rank and then weobtained a median rank (Median P-value rank across datasets). APOE showed asignificant up-regulation (fold change >1.5, P