Table 3 Prostate cancer extracellular vesicles as prognostic and monitoring biomarkers.

From: Extracellular vesicles as a source of prostate cancer biomarkers in liquid biopsies: a decade of research

Biomarker

Biofluid

EV isolation

Target detection

Number of patients

Comparison

Performance

Ref.

mRNAs

AR-V7

Plasma

ExoRNeasy kit (Qiagen)

ddPCR

36 mCRPC before second-line hormonal treatment

AR-V7+ vs. AR-V7-

PFT 3 vs. 20 months,

OS not reached vs. 8 months

[221]

9 CRPC, 7 HSPC

5 healthy men

PCa vs. healthy

Similar level of AR-V7 expression in EVs

[222]

Exoquick

(System Biosciences)

35 CRPC

AR-V7+ vs. AR-V7-

PFT 16 vs. 28 months

[219]

AR-V7/AR-FL ratio

Urine

Exo-Hexa

ddPCR

22 HSPC, 14 CRPC 11 healthy men

CRPC vs. HSPC

AUC 0.87

[223]

Plasma

ExoRNeasy kit (Qiagen)

73 CRPC

AR-V7+ vs. AR-V7-

PFS 4 vs. 20 months

OS not reached vs. 9 months

[218]

CD44v8–10

Serum

ExoRNeasy kit (Qiagen)

ddPCR

50 docetaxel naive 10 docetaxel resistant

15 healthy men

Docetaxel resistant vs. docetaxel naive

46 vs. 12 copies/ml (p = 0.032)

[226]

Docetaxel resistant vs. healthy men

46 vs. 17 copies/ml (p = 0.032)

BRN4

BRN2

Serum

Total exosome isolation reagent (Life Technologies)

RT-qPCR

42 mCRPC

6 mCRPC with NED

mCRPC-NE vs. mCRPC

Higher levels of BRN4 and BRN2 in mCRPC-NE:

EV-BRN4 AUC 1

EV- BRN2 AUC 0.944

[228]

42 mCRPC

6 mCRPC with NED

23 CRPC

mCRPC with enz. vs. mCRPC wo enz.

EV-BRN4 FC ≈ 7 (p < 0.0001)

EV-BRN2 FC ≈ 4 (p < 0.0001)

CK-8

Plasma

ExoRNeasy kit (Qiagen)

RT-qPCR

62 mCRPC

10 healthy men

Positive vs. negative

OS 16.9 vs. 31.8 months (p = 0.001)

[210]

LASSO

criteria (36 different mRNAs)

Urine

Microfiltration

Nanostring expression

Discovery cohort: 535 PCa

Diagnostic cohort: 177 PCa

Prognostic cohort: 87 PCa

D’Amico classification (normal vs. low vs. medium vs. high risk)

Model predicted the presence of clinically significant intermediate‐ or high‐risk disease. AUC 0.77

[214]

Able to detect BCR with HR 2.86 (p < 0.001)

miRNAs

miR-375

miR-1290

Plasma

Exoquick

(System Biosciences)

NGS

RT-qPCR

Discovery cohort:

23 mCRPC

Validation cohort:

100 mCRPC

High vs. low miR-375 and miR-1290 levels

OS 7.23 vs. 19.3 months

miRNAs + PSA + ADT failure time predict OS with AUC 0.73

[209]

miR-141

miR-375

Serum

ExoMiR extraction kit

(Bioo Scientific)

RT-qPCR

47 recurrent PCa,

72 non-recurrent PCa

Recurrent PCa vs. non-recurrent PCa

Increased levels in metastasis (p < 0.0001)

[179]

miR-151a

miR-204

miR-222

miR-23b

miR-331

PSA

Urine

miRCury exosome isolation kit (Qiagen)

RT-qPCR

Discovery cohort: 215 RP

Validation cohorts:

Cohort 2: 199 RP

Cohort 3: 205 RP

Pre- vs. post- RT

Predictor of BCR

Discovery: HR 3.12, (p < 0.001)

Cohort 2 HR 2.24 (p = 0.002)

Cohort 3: HR 2.15 (p = 0.004)

[215]

Proteins and other molecules or EV quantification methods

ACTN4

Serum

Ultracentrifugation

Proteomic analysis

36 PCa (8 untreated, 8 ADT, 20 CRPC different therapies)

CRPC vs. ADT

FC 1.4 (p < 0.01)

[227]

GSTP1 and RASSF1A methylation

Plasma

ExoRNeasy kit (Qiagen)

RT-qPCR

62 mCRPC

10 healthy men

Positive vs. negative

GSTP1 OS 8.6 vs. 21.4 months (p = 0.015)

RASSF1A OS 8.0 vs. 22.6 months (p = 0.007)

[210]

Vesicle amount

Serum

Total exosome isolation kit (Invitrogen)

RT-qPCR

11 PCa GS ≥ 7

Post- vs. pre-RT

FC 1.3 (p < 0.52)

[225]

Plasma

Antibody-captured

Nanoscale FACS

265 PCa, 67 mCRPC, 156 BPH, 22 healthy men

mCRPC vs. PCa

Higher levels of PSMA+ EVs in mCRPC

[211]

GS ≤ 7 vs GS ≥ 8

Higher levels of PSMA+ EVs in GS ≥ 8

25 mCRPC

Pre-RP vs. post-RP

Higher levels PSMA+ EVs in pre-RP

Blood

Antibody-captured

ACCEPT

software image analysis

190 CRPC

Low vs. high amount of EVs

OS 31.6 vs. 14.7 months

HR 2.2 (p = 0.001)

[213]

Blood

Antibody-captured

ACCEPT

Software image analysis

Discovery:

84 mCRPC

Validation:

45 mCRPC

93 Healthy men

Low vs. high amount of EVs

OS 23 vs. 8.1 months (p < 0.001)

HR 3.8 (p < 0.001)

[212]

  1. Only studies with more than 10 individuals were included in the table.
  2. ADT androgen-deprivation therapy, AR androgen receptor, AUC area under the curve, BCR biochemical recurrence, BPH Benign prostate hyperplasia, CI confidence interval, CRPC Castration-resistant prostate cancer, CTCs circulating tumour cells, ddPCR digital-droplet PCR, enz. Enzatulamide, EV extracellular vesicles, FL full-length, GS Gleason score, HR Cox hazard ratio, HSPC hormone-sensitive prostate cancer, mCRPC metastatic castration-resistant prostate cancer, NED neuroendocrine differentiation, OS overall survival, PCa prostate cancer, PFS progression-free survival, PSA prostate-specific antigen, RP radical prostatectomy, RT radiation therapy, v7 Variant 7, vs. versus, wo without.
Back to article page