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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
"ovarian carcinoma"
symptom
severe combined immunodeficiency
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