Unraveling the Role of EV-Derived miR-150-5p in Prostate Cancer Metastasis and Its Association with High-Grade Gleason Scores: Implications for Diagnosis
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Tissue and Plasma Collection
2.2. Cell Culture and Conditioned Media Collection
2.3. Microarrays from Paraffin Tissues and Plasma Samples
2.4. Ultracentrifugation for EV Isolation
2.5. Aqueous Two-Phase Separation for EV Isolation
2.6. Western Blot for EV Markers
2.7. Electron Microscopy for EVs
2.8. Nanoscale Flow Cytometry
2.9. RT-qPCR for miRNA Validation
2.10. Prediction of Target Genes and Cellular Pathways of Differentially Expressed miRNAs
3. Results
3.1. Differentially Expressed miRNAs in Metastatic Lymph Nodes
3.2. miRNAs from Metastatic Lymph Nodes Are Found in Plasma of PCa Patients
3.3. Validation of EVs Isolated from Conditioned Media
3.4. miRNAs Are Enriched in EVs from Tumoral and Non-Tumoral PCa Cell Lines
3.5. MiR-150-5p Is Associated with a High Gleason Score
3.6. MiR-150-5p Is Potentially Associated with Bone Metastasis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Total of Samples | Metastatic Lymph Node | Non-Metastatic Lymph Node | Tumor | |||
---|---|---|---|---|---|---|
n = 7 | n = 8 | n = 3 | ||||
Age | ||||||
Mean | 63.71 | 65.125 | 67.67 | |||
Range | 57–71 | 52–71 | 62–71 | |||
PSA (ng/mL) | ||||||
Mean | 15.64 | 13.06 | 18.18 | |||
Range | 8.35–27 | 8.13–18.11 | 9.43–27 | |||
Gleason Score | n | % | n | % | n | % |
3 + 3 | 3 | 42.86 | 3 | 37.50 | 2 | 66.67 |
3 + 4 | 1 | 14.29 | 3 | 37.50 | ||
4 + 3 | 1 | 12.50 | ||||
4 + 4 | 2 | 28.57 | 1 | 12.50 | 1 | 33.33 |
5 + 5 | 1 | 14.29 | ||||
Positive Nodes | ||||||
1–3 | 5 | 71.43 | ||||
4–6 | 1 | 14.29 | ||||
>7 | 1 | 14.29 |
Total of Samples ** | Prostate Cancer | Healthy Donors | |
---|---|---|---|
n = 16 | n = 10 | ||
Age | |||
Mean | 75.06 | 28.1 | |
Range | 55–93 | 22–45 | |
PSA (ng/mL) | |||
Mean | 84.72 | - | |
Range | 2.74–566 | - | |
Gleason Score * | n | % | |
3 + 3 | 4 | 57.14 | |
3 + 4 | 2 | 28.57 | |
4 + 3 | 1 | 14.29 | |
4 + 4 | 3 | 42.86 | |
4 + 5 | 1 | 14.29 | |
5 + 4 | 1 | 14.29 | |
5 + 5 | 2 | 28.57 | |
TNM Stage | n | % | |
T1A | 1 | 6.25 | |
T2A | 9 | 56.25 | |
T2B | 3 | 18.75 | |
T2C | 3 | 18.75 |
Tissue | miRNA | Fold Change | p-Value |
---|---|---|---|
Metastasis vs. Tumor | hsa-miR-150-5p | 30.81 | 0.003 |
hsa-miR-23b-3p | −2.03 | 0.0472 | |
hsa-miR-140-3p | 3.87 | 0.0213 | |
Metastasis vs. Lymph Node | hsa-miR-150-5p | No significant differential expression | |
hsa-miR-23b-3p | 2.36 | 0.0283 | |
hsa-miR-140-3p | No significant differential expression | ||
Tumor vs. Lymph Node | hsa-miR-150-5p | −23.14 | 0.0001 |
hsa-miR-23b-3p | 4.79 | 0.0009 | |
hsa-miR-140-3p | −3.8 | 0.0049 | |
PCa vs. Healthy Plasma | hsa-miR-150-5p | −2.47 | 0.0162 |
hsa-miR-23b-3p | −2.4 | 0.0308 | |
hsa-miR-140-3p | −1.63 | 0.0262 |
Total of Samples * | Prostate Cancer | Healthy Donors | |
---|---|---|---|
n = 31 | n = 12 | ||
Age | |||
Mean | 73.35 | 35.25 | |
Range | 57–86 | 26–45 | |
PSA (ng/mL) | |||
Mean | 16.709 | - | |
Range | 1.99–87.6 | - | |
Gleason Score | n | % | |
3 + 3 | 8 | 25.81 | |
3 + 4 | 7 | 22.58 | |
4 + 3 | 8 | 25.81 | |
4 + 4 | 4 | 12.90 | |
4 + 5 | 3 | 9.68 | |
5 + 5 | 1 | 3.23 |
Primary Tumor Tissue | Metastatic Lymph Node Tissue | Normal Prostate Tissue | ||||
---|---|---|---|---|---|---|
Total of samples | n = 15 | n = 5 | n = 20 | |||
Age | ||||||
Mean | 75.46 | 70.2 | 25.75 | |||
Range | 51–90 | 62–78 | 22–30 | |||
PSA (ng/mL) | ||||||
Mean | 33.2 | - | - | |||
Range | 0.7–106 | - | - | |||
Gleason Score * | n | % | Gleason Score | n | % | |
3 + 4 | 4 | 26.67 | 3 + 4 | - | - | |
4 + 3 | 3 | 20 | 4 + 3 | - | - | |
4 + 4 | - | - | 4 + 4 | 1 | 20 | |
4 + 5 | 3 | 20 | 4 + 5 | 2 | 40 | |
5 + 4 | 3 | 20 | 5 + 4 | 2 | 40 | |
5 + 5 | 1 | 6.67 | 5 + 5 | - | - | |
Stage ** | n | % | Number of Positive LNs | |||
IIB | 2 | 13.33 | 2 | 1 | 20 | |
IIIB | 2 | 13.33 | 4 | 1 | 20 | |
IIC | 1 | 6.67 | 6 | 2 | 40 | |
IIIC | 4 | 26.67 | 7 | 1 | 20 | |
IV | 3 | 20 |
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Cruz-Burgos, M.; Cortés-Ramírez, S.A.; Losada-García, A.; Morales-Pacheco, M.; Martínez-Martínez, E.; Morales-Montor, J.G.; Servín-Haddad, A.; Izquierdo-Luna, J.S.; Rodríguez-Martínez, G.; Ramos-Godínez, M.d.P.; et al. Unraveling the Role of EV-Derived miR-150-5p in Prostate Cancer Metastasis and Its Association with High-Grade Gleason Scores: Implications for Diagnosis. Cancers 2023, 15, 4148. https://doi.org/10.3390/cancers15164148
Cruz-Burgos M, Cortés-Ramírez SA, Losada-García A, Morales-Pacheco M, Martínez-Martínez E, Morales-Montor JG, Servín-Haddad A, Izquierdo-Luna JS, Rodríguez-Martínez G, Ramos-Godínez MdP, et al. Unraveling the Role of EV-Derived miR-150-5p in Prostate Cancer Metastasis and Its Association with High-Grade Gleason Scores: Implications for Diagnosis. Cancers. 2023; 15(16):4148. https://doi.org/10.3390/cancers15164148
Chicago/Turabian StyleCruz-Burgos, Marian, Sergio A. Cortés-Ramírez, Alberto Losada-García, Miguel Morales-Pacheco, Eduardo Martínez-Martínez, Jorge Gustavo Morales-Montor, Alejandro Servín-Haddad, J. Samuel Izquierdo-Luna, Griselda Rodríguez-Martínez, María del Pilar Ramos-Godínez, and et al. 2023. "Unraveling the Role of EV-Derived miR-150-5p in Prostate Cancer Metastasis and Its Association with High-Grade Gleason Scores: Implications for Diagnosis" Cancers 15, no. 16: 4148. https://doi.org/10.3390/cancers15164148