Transcriptomic profiling of urine extracellular vesicles reveals alterations of CDH3 in prostate cancer

Abstract

Extracellular vesicles (EV) are emerging structures with promising properties for intercellular communication. In addition, the characterization of EV in biofluids is an attractive source of non-invasive diagnostic, prognostic and predictive biomarkers. Here we show that urinary EV (uEV) from prostate cancer (PCa) patients exhibit genuine and differential physical and biological properties compared to benign prostate hyperplasia (BPH). Importantly, transcriptomics characterization of uEVs led us to define the decreased abundance of Cadherin 3, type 1 (CDH3) transcript in uEV from PCa patients. Tissue and cell line analysis strongly suggested that the status of CDH3 in uEVs is a distal reflection of changes in the expression of this cadherin in the prostate tumor. CDH3 was negatively regulated at the genomic, transcriptional, and epigenetic level in PCa. Our results reveal that uEVs could represent a non-invasive tool to inform about the molecular alterations in PCa.

Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression

“…Western-blot analysis showed that while we could not detect mitochondria (COX IV) or endoplasmic reticulum (GRP78) proteins, we could detect exosomal markers (CD10, CD63, CD9, Flotillin and CD26), and also some uromodulin (THP) (Supplementary Figure 1B). As previously, we found a high inter-individual variability in the abundance of these proteins [16,22]. In agreement with previous results [16], physical characterisation by NTA analysis of the isolated material revealed significant differences in the size distribution of particles isolated from PCa and BPH samples (Figure 1).…”

“…As previously, we found a high inter-individual variability in the abundance of these proteins [16,22]. In agreement with previous results [16], physical characterisation by NTA analysis of the isolated material revealed significant differences in the size distribution of particles isolated from PCa and BPH samples (Figure 1). Interestingly, the size of the particles increased with the stage of the PCa, thus, the major difference was observed between BPH and PCa stage 3 (Figure 1).…”

“…Then, an average curve was calculated for each group of patients to be compared among them. Cryo-electron microscopy and Western-blot analysis were performed as describe previously [16]. …”

Vesicle-MaNiA: extracellular vesicles in liquid biopsy and cancer

“…Some of these transcripts have differential abundance reminiscent of the prostate tumor. As an example, down-regulation of placental Cadherin (CDH3) in tumor tissue is recapitulated in mRNA from urine EVs [42]. This observation could open a new avenue on non-invasive characterization of transcriptional alterations with prognostic or therapeutic implications.…”

Comparative miRNA Analysis of Urine Extracellular Vesicles Isolated through Five Different Methods

“…These come mostly from renal and urethral cells [3], but also may filter directly from systemic circulation [4]. Therefore, unlike tissue biopsy, uEVs provide a full representation of the entire urinary system and can be used to provide markers for urinary tract conditions [3,5,6,7] as well as systemic conditions [4,8]. In the search for RNA biomarkers in urine, the study of uEVs is of particular importance, since they provide protection against degradation [9] in an environment with high RNAse [10] content.…”