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Up-regulation of 14-3-3ζ expression in intrahepatic cholangiocarcinoma and its clinical implications.
[cholangiocarcinoma]
The
14
-
3
-
3
proteins
are
highly
conserved
molecules
that
are
involved
in
many
vital
biologic
processes
and
are
associated
with
the
progression
of
cancer
.
The
role
of
14
-
3
-
3
ζ
,
a
dimeric
isoform
of
14
-
3
-
3
,
in
intrahepatic
cholangiocarcinoma
(
ICC
)
was
investigated
in
this
study
.
The
expression
of
14
-
3
-
3
ζ
in
tumour
samples
from
patients
with
ICC
was
examined
by
Western
blot
and
immunohistochemistry
,
and
the
correlation
between
its
expression
and
various
clinicopathological
features
was
determined
.
Then
,
the
capacity
for
invasion
,
migration
and
proliferation
as
well
as
the
expression
of
epithelial-mesenchymal
transition
(
EMT
)
-
related
markers
in
ICC
cells
were
assessed
after
14
-
3
-
3
ζ
depletion
.
Finally
,
the
prognostic
significance
of
14
-
3
-
3
ζ
in
patients
with
ICC
was
further
evaluated
by
Kaplan-
Meier
and
Cox
regression
analyses
.
The
expression
of
14
-
3
-
3
ζ
was
significantly
higher
in
ICC
tissues
compared
to
peritumoural
tissues
.
High
expression
of
14
-
3
-
3
ζ
positively
correlated
with
lymphatic
metastasis
and
tumour-node-metastasis
(
TNM
)
stage
.
The
inhibition
of
14
-
3
-
3
ζ
expression
was
able
to
impair
the
invasion
,
migration
and
proliferation
of
ICC
cells
in
vitro
.
The
expression
of
14
-
3
-
3
ζ
was
significantly
correlated
with
the
expression
of
the
EMT-related
markers
snail
and
E
-
cadherin
in
ICC
samples
.
Moreover
,
the
down-regulation
of
14
-
3
-
3
ζ
also
decreased
the
phosphorylation
of
extracellular
signal-regulated
kinase
(
ERK
)
in
ICC
cells
.
Clinically
,
patients
with
ICC
with
high
14
-
3
-
3
ζ
expression
demonstrated
a
poor
prognosis
in
terms
of
a
short
overall
survival
and
a
high
recurrence
rate
of
the
disease
.
A
multivariate
analysis
revealed
that
14
-
3
-
3
ζ
overexpression
was
an
independent
prognostic
indicator
for
patients
with
ICC
.
14
-
3
-
3
ζ
may
enhance
the
invasive
and
proliferative
capacity
of
tumour
cells
and
thus
prompt
the
progression
of
ICC
via
the
activation
of
ERK
signalling
and
the
induction
of
EMT
.
The
overexpression
of
14
-
3
-
3
ζ
may
be
used
as
a
prognostic
biomarker
and
therapeutic
target
in
patients
with
ICC
.
