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Exosome-derived miRNAs and ovarian carcinoma progression.
[severe combined immunodeficiency]
The
objective
of
this
study
was
to
analyze
the
expression
,
biological
role
and
clinical
relevance
of
exosomal
microRNAs
(
miRNAs
)
from
ovarian
carcinoma
(
OC
)
effusion
supernatants
.
Exosomal
miRNA
expression
profiling
was
performed
using
miRNA
Taqman
arrays
.
Selected
miRNAs
were
validated
using
quantitative
PCR
in
86
OC
effusion
supernatants
.
The
role
of
exosomal
miRNA
in
this
cancer
was
further
studied
using
in
vitro
and
in
vivo
models
.
miRNA
profiling
identified
99
miRNAs
with
high
expression
levels
in
exosomes
from
OC
effusion
supernatants
.
Quantitative
PCR
validation
of
11
miRNAs
showed
significant
associations
with
effusion
site
(
peritoneum
versus
pleura
)
and
International
Federation
of
Gynecology
and
Obstetrics
stage
.
In
univariate
survival
analysis
,
high
levels
of
miRNAs
21
,
23
b
and
29
a
were
associated
with
poor
progression-free
survival
(
P
=
0
.
01
,
P
=
0
.
015
and
P
=
0
.
009
,
respectively
)
,
whereas
high
expression
of
miRNA
21
correlated
with
poor
overall
survival
(
P
=
0
.
017
)
.
The
latter
association
was
retained
in
Cox
multivariate
analysis
(
P
=
0
.
001
)
.
Exposure
of
LP
9
mesothelial
cells
and
ES
2
OC
cells
to
OC
effusion-derived
exosomes
inhibited
tumor
spheroid
expansion
and
reduced
mesothelial
clearance
area
.
Treatment
of
severe
combined
immunodeficiency
mice
with
exosomes
from
OC
effusions
prior
to
injection
of
tumor
cells
was
associated
with
larger
tumor
load
,
more
infiltrative
tumors
and
shorter
survival
.
Patient-derived
OC
effusion
exosomes
contain
multiple
miRNAs
,
of
which
some
may
have
clinical
relevance
.
In
experimental
models
,
OC
exosomes
affect
both
tumor
cells
and
cells
in
the
tumor
microenvironment
and
induce
more
aggressive
disease
.
Collectively
,
these
data
demonstrate
the
central
role
of
miRNAs
and
their
content
in
the
biology
of
this
cancer
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated
