Identification of Filamin-A and -B as potential biomarkers for prostate cancer

Aim: A novel strategy for prostate cancer (PrCa) biomarker discovery is described. Materials & methods: In vitro perturbation biology, proteomics and Bayesian causal analysis identified biomarkers that were validated in in vitro models and clinical specimens. Results: Filamin-B (FLNB) and Keratin-19 were identified as biomarkers. Filamin-A (FLNA) was found to be causally linked to FLNB. Characterization of the biomarkers in a panel of cells revealed differential mRNA expression and regulation. Moreover, FLNA and FLNB were detected in the conditioned media of cells. Last, in patients without PrCa, FLNA and FLNB blood levels were positively correlated, while in patients with adenocarcinoma the relationship is dysregulated. Conclusion: These data support the strategy and the potential use of the biomarkers for PrCa. Lay abstract: The goal of this study was to use a novel strategy that combines biological outputs with Bayesian network learning to identify potential biomarkers for prostate cancer (PrCa). This methodology identified two proteins, filamin B and keratin-19, as potential biomarkers for PrCa. The network map also identified a direct linkage between filamin B and filamin A, which is a protein that has previously been identified as playing a role in PrCa etiology. The identified proteins were then validated by examining their levels in a panel of PrCa cell lines and in human plasma samples.