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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
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated
