Integrated Analysis of Single-Cell and Bulk RNA-Seq Data reveals that Ferroptosis-Related Genes Mediated the Tumor Microenvironment predicts Prognosis, and guides Drug Selection in Triple-Negative Breast Cancer
Опубликована: Май 12, 2025
Abstract
Background
Triple-negative
breast
cancer
(TNBC)
is
aggressive,
lacking
methods
to
predict
recurrence
and
drug
sensitivity.
Ferroptotic
heterogeneity
varies
in
TNBC
subtypes.
However,
the
tumor
microenvironment
(TME)
mediated
by
ferroptosis
genes
unclear.
Our
study
aims
integrate
single-cell
bulk
RNA
sequencing
(RNA-seq)
data
reveal
ferroptosis-mediated
TME
TNBC,
predicting
prognosis
guiding
treatment.
Methods
The
RNA-seq
of
were
sourced
from
Gene
Expression
Omnibus
(GEO)
database.
Using
these
data,
a
machine
learning
algorithm
was
employed
analyze
characteristics
ferroptosis-related
TNBC.
Prediction
models
for
survival
treatment
response
established
then
validated
an
independent
set.
Results
At
individual
cell
level,
T
cells
categorized
into
three
distinct
subpopulations,
local
macrophages
two
subpopulations.
infiltration
degree
different
subpopulations
closely
associated
with
outcomes.
Based
on
this,
risk
score
model
we
developed
effectively
predicted
recurrence-free
patients,
independently
pooled
3-,
4-,
5-year
Area
Under
Curves
(AUCs)
0.65,
0.67,
0.71,
respectively.
Additionally,
found
that
patients
high-risk
group
may
be
more
responsive
27
drugs.
Conclusions
We
have
uncovered
immune
clusters
ferroptosis.
A
constructed
identify
which
can
assist
physicians
disease
monitoring
precision
therapy.
identified
hold
significant
potential
as
therapeutic
targets
patients.
Funding
This
project
funded
National
Natural
Science
Foundation
China
(81974268,
82472000,
82304151),
Talent
Incentive
Program
Cancer
Hospital
Chinese,
Academy
Medical
Sciences
(801032247),
Cooperation
Fund
CHCAMS
(CFA202202023),
open
Beijing
Key
Laboratory
Tumor
Invasion
Metastasis
Mechanism,
Capital
University(2023ZLKF03).
Impact
Statement
Integrating
elucidates
role
offering
prognostic
personalized
insights.
Язык: Английский
Ferroptosis-related genes mediate tumor microenvironment and prognosis in triple-negative breast cancer via integrated RNA-seq analysis
eLife,
Год журнала:
2025,
Номер
13
Опубликована: Июнь 2, 2025
Triple-negative
breast
cancer
(TNBC),
an
aggressive
malignancy
with
limited
tools
to
predict
recurrence
and
drug
sensitivity,
exhibits
ferroptotic
heterogeneity
across
subtypes.
However,
the
tumor
microenvironment
(TME)
mediated
by
ferroptosis-related
genes
remains
poorly
characterized.
This
study
integrates
single-cell
bulk
RNA
sequencing
data
from
Gene
Expression
Omnibus
elucidate
ferroptosis-driven
TME
features
in
TNBC,
employing
machine
learning
develop
prognostic
therapeutic
response
prediction
models.
At
level,
T
cells
were
classified
into
three
subpopulations
macrophages
two
subpopulations,
their
infiltration
degrees
significantly
correlated
clinical
outcomes.
A
risk
score
model
constructed
based
on
these
findings
demonstrated
robust
predictive
performance,
validated
external
cohorts
3-,
4-,
5-year
area
under
receiver
operating
characteristic
curves
of
0.65,
0.67,
0.71,
respectively.
Notably,
high-risk
patients
exhibited
enhanced
sensitivity
27
agents.
By
delineating
ferroptosis-associated
immune
heterogeneity,
this
work
provides
a
stratification
tool
enhance
precision
decision-making
while
identifying
offer
actionable
targets
for
TNBC
medicine.
Язык: Английский