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Whole-miRNome profiling identifies prognostic serum miRNAs in esophageal adenocarcinoma: the influence of H. pylori infection status.
[esophageal adenocarcinoma]
Cell
free
circulating
microRNAs
(
cfmiRNAs
)
have
been
recognized
as
robust
and
stable
biomarkers
of
cancers
.
However
,
little
is
known
about
the
prognostic
significance
of
cfmiRNAs
in
esophageal
adenocarcinoma
(
EA
)
.
In
this
study
,
we
explored
whether
specific
cfmiRNA
profiles
could
predict
EA
prognosis
and
whether
H
.
pylori
(
HP
)
infection
status
could
influence
the
association
between
cfmiRNAs
and
EA
survival
outcome
.
We
profiled
1075
miRNAs
in
pooled
serum
samples
from
30
EA
patients
and
30
healthy
controls
.
The
most
relevant
cfmiRNAs
were
then
assessed
for
their
associations
with
EA
survival
in
an
independent
cohort
of
82
patients
,
using
Log-rank
test
and
multivariate
Cox
regression
models
.
qRT-PCR
was
used
for
cfmiRNA
profiling
.
HP
infection
status
was
determined
by
immunoblotting
assay
.
We
identified
a
panel
of
eighteen
cfmiRNAs
that
could
distinguish
EA
patients
from
healthy
subjects
(
P
=
3
.
0
E
-
12
)
.
In
overall
analysis
and
in
HP
-
positive
subtype
patients
,
no
cfmiRNA
was
significantly
associated
with
EA
prognosis
.
In
HP
-negative
patients
,
however
,
15
cfmiRNAs
were
significantly
associated
with
overall
survival
(
OS
)
(
all
P
<
0
.
05
)
.
A
combined
2
-
cfmiRNA
(
low
miR-
3935
and
high
miR-
4286
)
risk
score
was
constructed
that
showed
greater
risk
for
worse
OS
(
HR
=
2
.
22
,
P
=
0
.
0019
)
than
individual
cfmiRNA
alone
.
Patients
with
high
-risk
score
had
>
10
-
fold
increased
risk
of
death
than
patients
with
low
risk
score
(
P
=
0
.
0302
;
HR
=
10
.
91
,
P
=
0
.
0094
)
.
Our
findings
suggest
that
dysregulated
cfmiRNAs
may
contribute
to
EA
survival
outcome
and
HP
infection
status
may
modify
the
association
between
cfmiRNAs
and
EA
survival
.
Diseases
Validation
Diseases presenting
"overall survival"
symptom
cholangiocarcinoma
congenital diaphragmatic hernia
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
hodgkin lymphoma, classical
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