0.00E+00

5.00E+08

1.00E+09

1.50E+09

2.00E+09

2.50E+09

3.00E+09

3.50E+09

4.00E+09

4.50E+09

Normal BPH AggressivePCa

A

Size (nm)

Con

cent

ratio

n (E

6 pa

rticl

es/m

l)

100 200 300 400 500 600 700 800 900 1000

149.75BPH Aggressive PCa

Size (nm)

Con

cent

ratio

n (E

6 pa

rticl

es/m

l)

100 200 300 400 500 600 700 800 900 1000

128.27

CD63

TSG101

BPH Aggressive PCa

CB

0

20

40

60

80

100

120

Normal BPH AggressivePCa

Con

cent

ratio

n (E

6 pa

rticl

es/m

l)

Normal382.21

100 200 300 400 500 600 700 800 900 1000

Con

cent

ratio

n (E

6 pa

rticl

es/m

l)

Size (nm)

Fig. S1 Characterization of serum exosomal preparations

P=0.109

Siz

e (n

m)

P=0.376 P=0.472

P=0.216

BP

H1

BP

H2

BP

H3

PC

a1P

Ca2

PC

a3P

Ca4

PC

a5P

Ca6

D

024681012141618

11.2

11.3

11.4

11.5

11.6

11.7

11.8

ErbBreceptorsignalingnetwork

Plasmamembraneestrogenreceptorsignaling

Nectinadhesionpathway

IGF1pathway

LKB1signalingevents

Signalingevents

mediatedby

HepatocyteGrowthFactor

Receptor(c-Met)

TRAILsignalingpathway

IFN-gammapathway

-log1

0(p)

Perc

enta

ge o

f gen

es

Biological pathway

Percentage of genes p-value p=0.05 reference

Fig. S2 Biological pathways potentially influenced by dysregulated miRNAs in aggressive PCa as compared to BPH

A

0.001

0.01

0.1

1

10

100

1000 Exosomal Circulating

Rel

ativ

e ex

-miR

-124

6 ex

pres

sion

Samples

0

5

10

15

20

25

30

35

0 50 100 150 200 250

Circ

ulat

ing

miR

-124

6 ex

pres

sion

Exosomal miR-1246 expression

Correlation coefficient r: -0.157195% CI: -0.4897 to 0.2153P-value: 0.4070 (ns)

Fig. S3 Exosomal miR-1246 expression patterns differ from circulating miR-1246 expresssion in sera of prostate cancer patients

B

0

2

4

6

8

10

12

Cohort 2 Cohort 1 Cohort 3

Rel

ativ

e ex

-miR

-124

6 ex

pres

sion

Fig. S4 ex-miR-1246 expression as a measure of PCa aggressiveness

(Localized mets)

(Distant mets)

(No mets)

Aggressiveness