CONICET | Buscador de Institutos y Recursos Humanos

Proteomics represents an important tool for the identification of new molecular targets for prostate cancer (PCa) tailored therapy. Considering the heterogeneity of the prostate tumors, a single biomarker does not seem sufficient to predict the disease outcome. Towards this end, we undertook an in-depth mass spectrometry-based proteomics study to build the Heme-oxygenase 1 (HO-1) interactome in PCa. We have previously shown the anti-tumoral role of HO-1 in PCa. We propose that HO-1 and its interactors reprogram PCa cells and modify the tumoral microenvironment, favoring a less aggressive phenotype. FLAG immunoprecipitation assays were performed using lysates from PC3 cells transfected with FLAG-tagged HO-1, and the isolated proteins were subjected to LC/ESI-MSMS analysis. To address the relevance of the HO-1 interactome in prostate carcinogenesis we evaluated multiple microarray datasets for across the Oncomine database. We grouped the interactome in 3 clusters according to the following expression profiles: Cluster A- genes that were over or under-expressed in  60% of datasets, Cluster B- genes that were over or under-expressed in approx. 50% of datasets, Cluster C- genes that were over or under-expressed in similar percentages of datasets. Cluster A rendered the following genes: NOA1, CBX3, RCC1, EEF2, ASPH, SQSTM1, HSPB1 and ANXA2. Results show that for prostate adenocarcinoma vs. normal prostate gland these genes lie within 20 % of the most consistently high or low-expressed genes across this comparison. We selected cluster A for further analysis and assessed their expression profile across The Human Protein Atlas platform observing positive correlation for Cluster A genes compared to Oncomine. We also analyzed whole exome data for these genes (cBioportal) revealing amplification as the most frequent genetic alteration in the prostate cancer vs normal prostate comparison, ascertaining them as potential biomarker candidates for PCa.