Table 4.
Protein, miRNA, and mRNA biomarkers of urinary EVs for PCa.
| Type | Biomarker candidates | Assay | Area under curve (AUC) | Significance | Reference |
|---|---|---|---|---|---|
| Protein | |||||
| TM256 TM256+LAMTOR1 |
Liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS) | 0.87 0.94 |
Diagnosis | (94) | |
| Afamin, cardiotrophin-1, CDON, ARTS-1, FGF19, IL17RC, NAMPT, IL1RAPL2, CD226, IGFBP2, CCL16, TNFSF18, IGFBP5 |
SOMAscan®* | - | Prognosis | (99) | |
| FABP5 | iTRAQ-Labeling LC-MS/MS |
Gleason scores (GS)≥6: 0.757 GS≥7: 0.856 |
Diagnosis | (100) | |
| ADSV+TGM4 CD63+GLPK5+SPHM+PSA+PAPP |
SRM WB |
0.65 0.70 |
Diagnosis and prognosis | (101) | |
| Flotillin 2 Flotillin 2-PARK7 |
WB ELISA |
0.914 - |
Diagnosis | (102) | |
| FKBP5, FAM129A, RAB27A, FASN, NEFH |
LC-MS/MS | - | Diagnosis | (103) | |
| miRNA | |||||
| miR-19b | RT-qPCR | - | Diagnosis | (17) | |
| miR-204+miR-21+miR-375 miR-204+miR-21+miR-375+PSA |
Stemloop RT-PCR |
0.821 0.866 |
Diagnosis | (104) | |
| miR-574-3p miR-141-5p miR-21-5p |
RT-qPCR | 0.85 0.86 0.65 |
Diagnosis | (105) | |
| miR-21+miR-375 | RT-qPCR | 0.872 | Diagnosis and prognosis | (106) | |
| miR-196a-5p miR-501-3p |
RT-qPCR | 0.73 0.69 |
Diagnosis | (107) | |
| miR-2909 | RT-qPCR | - | Diagnosis and prognosis | (108) | |
| miR-145 miR-145+PSA |
RT-qPCR | 0.623 0.863 |
Diagnosis and prognosis | (109) | |
| 5 miRNA pairs (miR-30a: miR-125b; miR-425: miR-331; miR-29b: miR-21; miR-191: miR-200a; miR-331: miR-106b) |
miRCURY LNA miRNA qPCR Panels# | - | Diagnosis | (110) | |
| miR-375-3p+miR-574-3p | RT-qPCR | 0.744 | Diagnosis | (111) | |
| miR-6090/miR-3665 | Hydrogel-based hybridization chain reaction (HCR) | 0.88 | Diagnosis | (112) | |
| miR-30b-3p miR-12b-3p |
Microarray analysis; RT-qPCR | 0.663 0.664 |
Diagnosis | (113) | |
| miR-636+miR-21+miR-451+PSA | RT-qPCR | 0.925 | Prognosis | (114) | |
| mRNA | |||||
| TMPRSS2: ERG TMPRSS2 BIRC5 ERG PCA3 |
RT-qPCR | 0.744 0.637 0.674 0.785 0.681 |
Diagnosis | (35) | |
| ERG+PCA3+SPDEF+Standard of Care (SOC) | RT-qPCR | 0.77 | Diagnosis | (115) | |
| ERG+PCA3+SOC | RT-qPCR | 0.803 | Diagnosis | (34) | |
| CDH3 | RT-qPCR | - | Diagnosis | (116) | |
| GATA2 GATA2+PCA3+TMPRSS2-ERG |
RT-qPCR | 0.78(training) 0.65(validation) 0.85(training) 0.71(validation) |
Diagnosis | (117) | |
| PCA3+PCGEM1 | ddPCR | 0.88 | Diagnosis | (118) | |
*
A multiplex assay method consists of 1,129 individual affinity molecules called SOMAmer® reagents.
EVs, extracellular vesicles; AUC, area under curve; Ref, reference; ITRAQ, isobaric tags for relative and absolute quantitation; LC-MS/MS, liquid chromatograph-mass spectrometer/mass spectrometer; GS, Gleason scores; SRM, selected reaction monitoring; WB, western blotting; ELISA, enzyme-linked immunosorbent assay; RT-qPCR, reverse-transcription quantitative real-time PCR; PSA, prostate-specific antigen; HCR, hybridization chain reaction; SOC, standard of care; ddPCR, droplet digital PCR.