Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Янв. 16, 2023
Abstract
As
genomic
analysis
technology
has
advanced,
it
become
possible
to
sub-classify
intrahepatic
cholangiocarcinoma
(ICC)
at
the
histological
or
molecular
level.
Here,
we
verify
recently
suggested
two
subgroups
of
ICC
in
organoids
model,
compare
characteristics
between
types.
patients
are
subclassified
into
small-duct
(SD)
and
large-duct
(LD)
subtype
according
characteristics.
established,
unsupervised
principal
component
clustering
separates
each
type
ICC.
Differential
gene
expression
reveals
enrichment
on
KRAS,
TGFβ
ERBB2
signaling
pathways
LD-type
compared
with
SD-type
(
P
<
0.05).
Gene
set
demonstrates
that
class
2
signature,
defined
by
Andersen
et
al.,
is
enriched
(enrichment
Score
=
2.19,
0.001).
A
protein-protein
interaction
network
identifies
ZNF217
as
a
significant
hub
protein
(odds
ratio
4.96,
0.0105).
We
perform
prospective
modeling
using
patient-derived
organoids.
Moreover,
profiling
enables
identification
type-specific
targetable
pathways.
Cell Reports,
Год журнала:
2019,
Номер
27(4), С. 1265 - 1276.e4
Опубликована: Апрель 1, 2019
Biliary
tract
carcinomas
(BTCs)
are
among
the
most
aggressive
malignancies
and
have
a
poor
prognosis.
Here,
we
successfully
established
organoid
lines
derived
from
intrahepatic
cholangiocarcinoma,
gallbladder
cancer,
neuroendocrine
carcinoma
of
ampulla
Vater.
These
organoids
BTCs
were
cultured
stably
for
>1
year
closely
recapitulated
histopathology,
gene
expression,
genetic
alterations
evident
in
primary
tumors.
Gene
expression
profiling
revealed
that
SOX2
could
be
potential
prognostic
biomarker
patients
with
BTC.
We
screened
compound
library
consisting
drugs
used
clinically
their
ability
to
suppress
found
antifungal
amorolfine
fenticonazole
significantly
suppressed
growth
minimal
toxicity
normal
biliary
epithelial
cells.
Patient-derived
may
powerful
research
tool
clarification
molecular
pathogenesis
discovery
biomarkers
therapeutic
refractory
cancers.
Pathologica,
Год журнала:
2021,
Номер
113(3), С. 158 - 169
Опубликована: Июнь 1, 2021
Liver
cancer
represents
the
third
leading
cause
of
cancer-related
death
worldwide.
Cholangiocarcinoma
(CCA)
is
second
most
common
type
liver
after
hepatocellular
carcinoma,
accounting
for
10-15%
all
primary
malignancies.
Both
incidence
and
mortality
CCA
have
been
steadily
increasing
during
last
decade.
Moreover,
CCAs
are
diagnosed
at
an
advanced
stage,
when
therapeutic
options
very
limited.
may
arise
from
any
tract
biliary
system
it
classified
into
intrahepatic,
perihilar,
distal
CCA,
according
to
anatomical
site
origin.
This
topographical
classification
also
reflects
distinct
genetic
histological
features,
risk
factors,
clinical
outcomes.
review
focuses
on
histopathology
its
differential
diagnoses,
diagnostic
pitfalls.
Hepatology,
Год журнала:
2021,
Номер
74(3), С. 1429 - 1444
Опубликована: Март 25, 2021
Genetic
alterations
in
intrahepatic
cholangiocarcinoma
(iCCA)
are
increasingly
well
characterized,
but
their
impact
on
outcome
and
prognosis
remains
unknown.This
bi-institutional
study
of
patients
with
confirmed
iCCA
(n
=
412)
used
targeted
next-generation
sequencing
primary
tumors
to
define
associations
among
genetic
alterations,
clinicopathological
variables,
outcome.
The
most
common
oncogenic
were
isocitrate
dehydrogenase
1
(IDH1;
20%),
AT-rich
interactive
domain-containing
protein
1A
(20%),
tumor
P53
(TP53;
17%),
cyclin-dependent
kinase
inhibitor
2A
(CDKN2A;
15%),
breast
cancer
1-associated
(15%),
FGFR2
polybromo
(12%),
KRAS
(10%).
IDH1/2
mutations
(mut)
mutually
exclusive
fusions,
neither
was
associated
For
all
patients,
TP53
(P
<
0.0001),
CDKN2A
0.0001)
predicted
worse
overall
survival
(OS).
These
high-risk
enriched
advanced
disease
adversely
impacted
across
stages,
even
when
controlling
for
known
correlates
(multifocal
disease,
lymph
node
involvement,
bile
duct
type,
periductal
infiltration).
In
resected
209),
TP53mut
(HR,
1.82;
95%
CI,
1.08-3.06;
P
0.03)
deletions
(del;
HR,
3.40;
1.95-5.94;
0.001)
independently
shorter
OS,
as
did
clinical
variables
liver
[P
0.001];
regional
metastases
0.001]),
whereas
KRASmut
1.69;
0.97-2.93;
0.06)
trended
toward
statistical
significance.
presence
both
or
factors
represented
extremes
(median
18.3
vs.
74.2
months;
0.001),
alone
38.6
28.8-73.5)
37.0
27.6-not
available)
intermediate
TP53mut,
KRASmut,
CDKN2Adel
similarly
unresectable
iCCA.
features
notable
limited
no
benefit
resection
over
chemotherapy.TP53,
KRAS,
independent
prognostic
pathologic
stage,
treatment.
Because
profiling
can
be
integrated
into
pretreatment
therapeutic
decision-making,
combining
may
identify
patient
subgroups
poor
irrespective
treatment
strategy.
