Extracellular Vesicle Proteome in Prostate Cancer: A Comparative Analysis of Mass Spectrometry Studies

Figures

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  Figure 1. Systematic representation of the present and future possibilities for diagnosis of the PCa. The upper left panel highlights current limitations in screening methods. The lower left panel indicates future possibilities for EV based diagnostics and especially uEVs for PCa detection which will be further discussed in this study. The right panel indicates current diagnostics methods. CTCs: circulating tumor cells, cfDNA/cfRNA: cell free DNA/RNA, DRE: digital rectal examination, TRUS: transrectal ultrasound, and MRI: Magnetic Resonance Imaging.

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  Figure 2. Exosomes biogenesis. Multivesicular endosomes in the cell which are produced by the invagination of endosomal limiting membrane and can secrete their content as exosomes or fuse with lysosomes to originating endolysomes.

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  Figure 3. Functional effects described in the literature for PCa EVs.

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  Figure 4. Photomicrograph of a prostatic acinar adenocarcinoma with multiple morphological patterns, such as some uniform medium sized glands (blue arrowhead), small poorly-formed and fused glands (black arrowhead) and both large and small round cribriform glands (arrows) with well-formed lumina (H&E, 10×). Image provided by João Pimentel MD, Pathology Department, Centro Hospitalar e Universitário Lisboa Central, October 2021.

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  Figure 5. Overview of omics technologies applied in PCa using different biopsy samples. (A) The proportion of different omics technology based studies applied to each biopsy sample type are indicated on the y axis and the total numbers in the lower bars. (B) Number of retrieved PubMed studies in PCa for each omics technology and biopsy sample type. Abbreviations: expressed prostatic secretions (EPS), seminal plasma (SP) and extracellular vesicles (EV).

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  Figure 6. Network analysis depicting the proteins proposed as biomarkers by different studies in the intersections. The node sizes correlate with the number of potential biomarkers or prostate enriched proteins proposed in the studies: Kawahara 2019 [90], Dhondt 2020 [82], Fujita 2017 [113], Turiak 2019 [91], Zhang 2020 [87], Bijnsdorp 2013 [114], Iglesias-Gato 2016 [85], Principe 2012 [84], and Sequeiros 2017 [18]. The vertex thicknesses correlate with log10 of the number of proteins in the intersection. The actual proteins in the intersections were depicted for EV studies in which the proposed markers were validated. The term “pre” indicates samples from patients previous to treatment and “post” after treatment.

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  Figure 7. KEGG functional enrichment analysis of (a) significantly down- and (b) significantly up-regulated proteins in cancer compared to control cases. Significantly regulated proteins were defined as adjusted p value less than 0.05. B indicates benign.