Kidney
renal
clear
cell
carcinoma
(KIRC)
is
one
of
the
most
prevalent
malignant
tumors
urinary
system,
with
a
high
recurrence
and
metastasis
rate.
Telomeres
long
non-coding
RNAs
(lncRNAs)
have
been
documented
playing
critical
roles
in
cancer
progression.
However,
prognostic
significance
telomere-related
lncRNA
(TRLs)
KIRC
less
well-defined.
The
Cancer
Genome
Atlas
database
was
applied
to
retrieve
expression
profiles
corresponding
clinical
information
patients.
To
create
TRLs
signature,
univariate
Cox
regression,
least
absolute
shrinkage
selection
operator
analyses
were
performed.
comprised
nine
TRLs,
developed
demonstrated
superior
ability
for
Additionally,
risk
score
acted
as
an
independent
indicator.
A
nomogram
incorporating
age,
grade,
stage,
signature-based
scores
also
exhibited
excellent
predictive
accuracy.
Several
immune
activities
associated
determined
by
gene
function
analysis.
Further
analysis
revealed
differences
status
immunity
tumor
microenvironment
between
low-
high-risk
groups.
Notably,
patients
more
responsive
immunotherapy
chemotherapy.
summarize,
our
study
new
signature
consisting
that
can
precisely
predict
prognosis
shown
be
substantial
value
mutation
burden,
thereby
contributing
framework
individualized
treatment
Cancer Cell International,
Год журнала:
2025,
Номер
25(1)
Опубликована: Апрель 9, 2025
Hepatocellular
carcinoma
(HCC)
is
the
main
phenotype
of
liver
cancer
with
a
poor
prognosis.
Copper
vital
in
function,
and
HCC
cells
rely
on
it
for
growth
metastasis,
leading
to
cuproplasia.
Excessive
copper
can
induce
cell
death,
termed
cuproptosis.
Tumor
microenvironment
(TME)
pivotal
HCC,
especially
immunotherapy,
closely
related
TME
pathogenesis.
However,
how
these
two
mechanisms
contribute
intriguing.
We
conducted
latest
progress
literature
cuproplasia
cuproptosis
summarized
their
specific
roles
treatment
strategies.
The
relationship
role
have
been
deeply
summarized.
Cuproplasia
fosters
formation,
angiogenesis,
whereas
may
alleviate
mitochondrial
dysfunction
hypoxic
conditions
TME.
Inhibiting
enhancing
are
essential
achieving
therapeutic
efficacy
HCC.
An
in-depth
analysis
within
unveils
opposing
nature
impact
regulation.
Grasping
equilibrium
between
factors
crucial
deeper
understanding
shed
light
novel
directions
treating
World Journal of Oncology,
Год журнала:
2022,
Номер
13(5), С. 299 - 310
Опубликована: Окт. 1, 2022
Background:
Hepatocellular
carcinoma
(HCC)
is
the
most
common
type
of
liver
cancers,
with
more
than
a
million
cases
per
year
by
2025.
Cuproptosis
novel
form
programmed
cell
death,
and
caused
mitochondrial
lipoylation
destabilization
iron-sulfur
proteins
triggered
copper,
which
was
considered
as
key
player
in
various
biological
processes.
However,
roles
cuproptosis-related
genes
(CRGs)
HCC
remain
largely
unknown.
Methods:
In
present
study,
we
constructed
validated
four
CRGs
signature
for
predicting
overall
survival
(OS)
patients
both
The
Cancer
Genome
Atlas
(TCGA)
International
Consortium
(ICGC)
databases.
Results:
Patients
high
risk
score
showed
shorter
OS
those
low
score.
Functional
analysis
suggested
that
CRGs-based
prognostic
associated
metabolism
remodeling
facilitated
cancer
progression.
addition,
reduced
infiltration
CD8
+
T
cells
increased
macrophages
were
found
HCCs
from
As
one
CRGs,
higher
expression
dihydrolipoamide
S-acetyltransferase
(DLAT)
accompanied
program
death
ligand
1
(PD-L1)
HCC.
Further,
confirmed
DLAT
up-regulated
correlated
poor
prognosis
clinical
cohort.
Conclusion:
conclusion,
our
study
model
identified
an
independent
factor
HCC,
thus
providing
new
clues
understanding
association
between
cuproptosis
World
J
Oncol.
2022;13(5):299-310
doi:
https://doi.org/10.14740/wjon1529
Cancer Medicine,
Год журнала:
2023,
Номер
12(7), С. 8991 - 9004
Опубликована: Янв. 20, 2023
Abstract
Background
Hepatocellular
carcinoma
(HCC)
is
one
of
the
major
causes
cancer‐related
deaths
globally.
The
tumor
microenvironment
(TME)
plays
a
crucial
role
in
prognosis
and
treatment
HCC.
Hence,
it
important
to
exploit
new
biomarkers
for
survival
surveillance
TME
estimation
Methods
HCC
samples
data
was
collected
from
Cancer
Genome
Atlas
(TCGA)
International
Consortium
(ICGC)
database,
clinical
were
our
center.
explored
with
ESTIMATE
(Estimation
STromal
Immune
cells
MAlignant
Tumor
tissues
using
Expression
data),
ssGSEA
(single
sample
Gene
Sets
Enrichment
Analysis)
CIBERSORT
algorithm.
Differentially
expressed
genes
analyzed
functional
enrichment
analysis.
Immunohistochemistry
implemented
validate
results.
Results
Based
on
TCGA
we
found
that
Neutrophil
Cytosolic
Factor
2
(NCF2)
significantly
associated
patients,
involved
immune‐related
biological
processes
closely
some
types
immunocompetent
cells.
analysis
based
NCF2
expression
assessed
by
immunohistochemistry
also
confirmed
NCF2‐positive
group
had
shorter
relapse
free
(RFS)
overall
(OS)
than
NCF2‐negative
group.
Multivariate
Cox
regression
revealed
level
lymphovascular
space
invasion
(LVSI)
independent
risk
factors
patients.
Receiver
operating
characteristic
curves
showed
combination
LVSI
higher
predictive
efficacy
1‐year
RFS
rate
5‐year
OS
each
them
alone.
Besides,
positively
M0
M2
macrophages
infiltration.
Furthermore,
correlated
CSF1,
IL4,
IL10,
CD206,
CD163,
CSF1R
TGFβ1.
Conclusion
We
proposed
predicted
an
adverse
more
infiltration
Hepatocellular
carcinoma
(HCC)
is
a
common
abdominal
cancer
with
dissatisfactory
therapeutic
effects.
The
discovery
of
cuproptosis
lights
on
new
approach
for
treatment
and
assessment.
So
far,
there
extremely
limited
research
investigating
the
roles
cuproptosis-related
(CR)
genes
in
cancers.A
novel
CR
risk
signature
was
constructed
using
Lasso
regression
analysis.
Its
prognostic
value
assessed
via
series
survival
analyses
validated
three
GEO
cohorts.
effects
tumor
immune
microenvironment
(TIM)
were
explored
through
CIBERSORT,
ESTIMATE,
ssGSEA
algorithms.
Using
GESA,
we
investigated
its
impacts
various
metabolism
process.
somatic
mutation
features
also
cBioPortal
database.
burden,
expressions
checkpoints,
TIDE
score,
IMvigor
210
cohort,
GSE109211
dataset,
potential
associations
score
efficacy
checkpoint
inhibitors
(ICIs)
sorafenib.
Finally,
biofunctions
DLAT
HCC
cells
ascertained
qPCR,
immunohistochemistry,
colony
formation,
Transwell
assays.FDX1,
DLAT,
CDKN2A
GLS
constituted
signature.
possessed
high
applicable
to
validation
Meanwhile,
it
could
improve
accuracy
clinical
making-decision
benefit
traditional
model.
Moreover,
indicative
unfavorable
anti-tumor
response
active
metabolisms
glycolysis
nucleotide.
As
correlation,
biomarker
predicting
ICIs
Through
qPCR
immunohistochemistry
detection
samples,
reconfirmed
significantly
upregulated
samples.
Overexpression
promote
proliferation,
migration,
invasion
HepG2
HuH-7
cells.The
greatly
contributed
assessment
HCC.
Cuproptosis
regulatory
gene
cancer-promoting
capacities
expected
be
promising
target
BMC Gastroenterology,
Год журнала:
2024,
Номер
24(1)
Опубликована: Апрель 23, 2024
Abstract
Objectives
Cuproptosis
represents
an
innovative
type
of
cell
death,
distinct
from
apoptosis,
driven
by
copper
dependency,
yet
the
involvement
apoptosis-associated
long
non-coding
RNAs
(CRLncRNAs)
in
hepatocellular
carcinoma
(HCC)
remains
unclear.
This
study
is
dedicated
to
unveiling
role
and
significance
these
apoptosis-related
lncRNAs
within
context
HCC,
focusing
on
their
impact
both
development
disease
its
prognosis.
Methods
We
conducted
analysis
gene
transcriptomic
clinical
data
for
HCC
cases
sourcing
information
The
Cancer
Genome
Atlas
database.
By
incorporating
cuproptosis-related
genes,
we
established
prognostic
features
associated
with
lncRNAs.
Furthermore,
elucidated
mechanism
prognosis
treatment
through
comprehensive
approaches,
including
Lasso
Cox
regression
analyses,
survival
analyses
samples,
as
well
examinations
tumor
mutation
burden
immune
function.
Results
developed
a
model
featuring
six
lncRNAs:
AC026412.3,
AC125437.1,
AL353572.4,
MKLN1-AS,
TMCC1-AS1,
SLC6A1-AS1.
demonstrated
exceptional
accuracy
training
validation
cohorts
patients
tumors,
showing
significantly
longer
times
those
categorized
low-risk
group
compared
high-risk
group.
Additionally,
our
burden,
function,
Gene
Ontology,
Kyoto
Encyclopedia
Genes
Genomes
pathway
enrichment,
drug
sensitivity,
further
potential
mechanisms
which
cuproptosis-associated
may
influence
outcome.
Conclusions
using
(lncRNAs)
demonstrates
promising
predictive
capabilities
immunotherapy
outcomes
patients.
could
play
crucial
patient
management
optimization
immunotherapeutic
strategies,
offering
valuable
insights
future
research.
Cancers,
Год журнала:
2022,
Номер
14(22), С. 5713 - 5713
Опубликована: Ноя. 21, 2022
Background:
Studies
on
prognostic
potential
and
tumor
immune
microenvironment
(TIME)
characteristics
of
cuproptosis-related
genes
(CRGs)
in
hepatocellular
carcinoma
(HCC)
are
limited.
Methods:
A
multigene
signature
model
was
constructed
using
the
least
absolute
shrinkage
selection
operator
(LASSO)
Cox
regression
analysis.
The
multivariate
cox
analysis
bulk
RNA-seq-based
infiltration
were
performed.
results
verified
two
cohorts.
enrichment
CRGs
T
cells
based
single-cell
RNA
sequencing
(scRNA-seq)
Real-time
polymerase
chain
reaction
(RT-PCR)
multiplex
immunofluorescence
staining
performed
to
verify
reliability
conclusions.
Results:
four-gene
risk
scoring
constructed.
Kaplan−Meier
curve
showed
that
high-risk
group
had
a
worse
prognosis
(p
<
0.001).
time-dependent
receiver
operating
characteristic
(ROC)
OS
score
prediction
performance
good.
These
further
confirmed
validation
queue.
Meanwhile,
Tregs
macrophages
enriched
TIME
HCC.
Conclusions:
CRGs-based
could
predict
Treg
significantly
HCC,
which
associated
with
depletion
proliferating
cells.
Hepatocellular
carcinoma
(HCC)
is
a
prevalent
primary
liver
malignancy
and
leading
cause
of
cancer-related
mortality
worldwide.
Despite
advancements
in
therapeutic
strategies,
the
5-year
survival
rate
for
individuals
undergoing
curative
resection
remains
between
10%
15%.
Consequently,
identifying
molecular
targets
that
specifically
inhibit
proliferation
metastasis
HCC
cells
critical
improving
treatment
outcomes.
Database
analysis
using
Targetscan
identified
complementary
binding
sites
human-specific
miRNA
hsa-miR-6894-3p
(hereafter
referred
to
as
miR-6894-3p)
on
SHROOM2,
Starbase
data
suggested
potential
regulatory
interaction
lnc-MAP3K13-3:1
miR-6894-3p
cancer.
This
study
aimed
investigate
role
regulating
miR-6894-3p,
with
focus
its
impact
proliferation,
apoptosis,
migration,
related
cellular
processes
cancer
via
SHROOM2
regulation.
Quantitative
PCR
(qPCR)
was
initially
employed
measure
expression
levels
three
cell
lines:
HepG2,
HuH-7,
Li-7.
Based
these
initial
assessments,
two
lines
were
selected
further
experimentation.
Stable
overexpressing
developed,
transfected
mimics
or
mimic
negative
control
(NC).
After
24
h,
qPCR
utilized
quantify
relative
lnc-MAP3K13-3:1,
Caspase9
mRNA
each
group.
Cell
analyzed
counting
Kit-8
assay,
while
flow
cytometry
used
assess
cycle
distribution
apoptosis.
Migration
capabilities
evaluated
through
scratch
assays,
dual-luciferase
assays
verify
interactions
SHROOM2.
Overexpression
transfection
resulted
increased
mRNA,
demonstrated
by
qPCR.
The
regulated
activity
lnc-MAP3K13-3:1.
Functional
showed
overexpression
inhibited
HuH-7
Li-7
cells,
promoted
reduced
migration
but
enhanced
cells.
Additionally,
significantly
proportion
G2/M
phase
S
phase.
modulated
effects
migration.
Dual-luciferase
confirmed
direct
well
These
findings
indicate
regulates
targeting
thereby
influencing
other
associated
HCC.
Frontiers in Pharmacology,
Год журнала:
2022,
Номер
13
Опубликована: Дек. 14, 2022
Hepatocellular
carcinoma
(HCC)
is
one
of
the
world’s
malignant
tumors
with
high
morbidity
and
mortality.
Cuproptosis
a
novel
form
cell
death.
However,
prognostic
evaluation
immune
relevance
cuproptosis-related
genes
(CRGs)
in
HCC
are
largely
unknown.
In
our
study,
we
constructed
model
CRGs
performed
infiltration,
functional
analysis,
checkpoint
drug
sensitivity
analysis.
Systematically
elaborated
correlation
HCC.
The
results
showed
that
15
were
up-regulated
or
down-regulated
HCC,
mutation
frequency
reached
10.33%
CDKN2A
having
highest
frequency.
These
19
mainly
involved
mitochondrion,
response
metabolic
pathways.
Five
selected
(CDKN2A,
DLAT,
DLST,
GLS,
PDHA1)
constructing
enables
overall
survival
patients
to
be
predicted
moderate
accuracy.
Prognostic
CRGs,
especially
CDKN2A,
independent
factor
prognosis,
may
closely
associated
immune-cell
tumor
burden
(TMB),
microsatellite
instability(MSI),
checkpoints.
CD274,
CTLA4,
LAG3,
PDCD1,
PDCD1LG2
SIGLEC15
identified
as
potential
therapeutic
targets
CD274
correlated
highly
genes.
Quantitative
Real-Time
PCR
(qRT-PCR)
immunohistochemical
validate
mRNA
protein
expression
levels
adjacent
normal
tissues
tissues,
consistent
gene
difference
conclusion,
serve
predictors
provide
insights
into
cancer
therapy.
Background
and
aims
Hepatocellular
carcinoma
(HCC)
is
a
common
cause
of
cancer-related
death
in
humans.
Increasing
evidence
indicates
that
an
imbalance
N6-methyladenosine
(m6A)
methylation
linked
to
the
occurrence
development
cancer.
We
then
developed
prognostic
model
as
independent
risk
factor
with
which
predict
prognosis
HCC.
Methods
obtained
gene
expression
clinical
data
HCC
patients
from
TCGA
databases.
The
value
m6A
methylation-related
genes
who
had
were
subjected
comprehensive
bioinformatics
analysis.
use
RiskScore=∑i=1nCoefi×Xi
construct
scoring
formula.
collected
pathological
specimens
68
HCC,
conducted
immunohistochemical
staining
experiments
on
specimens.
Results
There
was
significant
correlation
between
candidate
(YTHDF2,
METTL14
ZC3H13)
overall
survival
patients.
Among
patient
underwent
staining,
all
cancer
tissues
positive
for
METTL14,
YTHDF2,
ZC3H13
contrast
adjacent
tissues.
Kaplan-Meier
results
showed
low
longer
time
than
those
high
expression.
Also,
YTHDF2
Finally,
lived
This
result
consistent
analysis
conclusion
above.
Conclusions
Generally,
based
this
study
can
effectively