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Decrease of fibulin-3 in hepatocellular carcinoma indicates poor prognosis.
[werner syndrome]
Fibulin-
3
,
originally
identified
in
senescent
and
Werner
syndrome
fibroblasts
,
has
been
implicated
in
cell
morphology
,
growth
,
adhesion
and
motility
.
Fibulin-
3
exhibits
both
antitumor
and
oncogenic
activities
towards
human
cancers
;
however
,
the
role
of
Fibulin-
3
in
hepatocellular
carcinoma
(
HCC
)
remains
elusive
.
In
this
study
,
we
showed
that
both
the
mRNA
and
protein
levels
of
Fibulin-
3
were
remarkably
downregulated
in
HCC
cell
lines
and
fresh
tissues
.
Immunohistochemical
data
revealed
that
Fibulin-
3
was
decreased
in
tumorous
tissues
in
67
.
1
%
(
171
/
255
)
of
cases
compared
to
the
corresponding
adjacent
nontumorous
tissues
.
The
results
of
statistical
analysis
indicated
that
low
Fibulin-
3
expression
,
defined
by
the
receiver
operating
characteristic
curve
(
ROC
)
,
was
significantly
associated
with
tumor
differentiation
(
P
=
0
.
008
)
,
clinical
stage
(
P
=
0
.
014
)
and
serum
AFP
levels
(
P
<
0
.
01
)
.
Furthermore
,
Kaplan-
Meier
and
multivariate
analysis
suggested
that
Fibulin-
3
is
an
independent
negative
prognostic
indicator
for
both
overall
(
P
<
0
.
001
)
and
recurrence-free
(
P
=
0
.
036
)
survival
.
In
addition
,
an
in
vitro
study
demonstrated
that
knockdown
of
Fibulin-
3
by
siRNA
markedly
increased
cell
viability
and
promoted
cell
invasion
in
HCC
cells
.
Collectively
,
our
data
suggest
that
Fibulin-
3
exhibits
antitumor
effects
towards
HCC
and
serves
as
a
biomarker
of
unfavorable
prognosis
for
this
deadly
disease
.
Diseases
Validation
Diseases presenting
"independent negative prognostic indicator"
symptom
werner syndrome
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