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The prognostic significance of Smad3, Smad4, Smad3 phosphoisoform expression in esophageal squamous cell carcinoma.
[esophageal squamous cell carcinoma]
Smad
3
functions
as
an
integrator
of
diverse
signaling
,
including
transforming
growth
factor
β
signaling
and
the
function
of
Smad
3
is
complexly
regulated
by
differential
phosphorylation
at
various
sites
of
Smad
3
.
Despite
the
importance
of
Smad
3
and
its
various
phosphoisoforms
,
their
prognostic
significance
has
rarely
been
studied
.
In
this
study
,
we
demonstrated
the
prognostic
significance
of
Smad
3
,
its
phosphoisoforms
,
and
Smad
4
expression
by
immunohistochemistry
in
126
esophageal
squamous
cell
carcinomas
.
The
phosphoisoforms
of
Smad
3
studied
in
this
article
included
phosphorylation
at
C-
terminal
(
pSmad
3
C
)
(
Ser
(
423
/
425
)
)
and
phosphorylation
at
the
linker
region
(
pSmad
3
L
)
(
Ser
(
213
)
)
.
High
expression
of
Smad
3
was
associated
with
shorter
overall
survival
.
Co
-existence
of
high
expression
of
pSmad
3
L
(
S
213
)
and
low
expression
of
pSmad
3
C
(
S
423
/
425
)
were
associated
with
advanced
N
stage
and
an
independent
prognostic
factor
for
overall
[
hazard
ratio
(
HR
)
2
.
03
,
95
%
confidence
interval
(
CI
)
(
1
.
10
-
3
.
75
)
,
p
=
0
.
023
]
and
disease-free
survival
[
HR
2
.
41
,
95
%
CI
(
1
.
32
-
4
.
39
)
,
p
=
0
.
004
]
.
In
conclusion
,
co
-existence
of
high
pSmad
3
L
(
Ser
(
213
)
)
expression
and
low
pSmad
3
C
(
Ser
(
423
/
425
)
)
expression
can
be
considered
as
immunohistochemical
biomarkers
for
predicting
prognosis
as
well
as
future
therapeutic
targets
.
In
addition
,
our
results
of
combinatory
effect
of
differential
phosphorylation
of
Smad
3
on
prognosis
suggest
the
mode
of
action
of
Smad
3
might
be
logically
determined
by
its
phosphorylation
pattern
.
Diseases
Validation
Diseases presenting
"high expression"
symptom
carcinoma of the gallbladder
cholangiocarcinoma
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
gm1 gangliosidosis
hodgkin lymphoma, classical
malignant atrophic papulosis
phenylketonuria
primary effusion lymphoma
severe combined immunodeficiency
waldenström macroglobulinemia
wiskott-aldrich syndrome
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