Abstract
Malignant
tumors
have
increasing
morbidity
and
high
mortality,
their
occurrence
development
is
a
complicate
process.
The
of
sequencing
technologies
enabled
us
to
gain
better
understanding
the
underlying
genetic
molecular
mechanisms
in
tumors.
In
recent
years,
spatial
transcriptomics
been
developed
rapidly
allow
quantification
illustration
gene
expression
context
tissues.
Compared
with
traditional
technologies,
not
only
detect
levels
cells,
but
also
inform
location
genes
within
tissues,
cell
composition
biological
interaction
between
cells.
Here
we
summarize
tools
its
application
cancer
research.
We
discuss
limitations
challenges
current
approaches,
as
well
future
prospects.
Cellular Signalling,
Год журнала:
2025,
Номер
127, С. 111606 - 111606
Опубликована: Янв. 13, 2025
Clear
cell
renal
carcinoma
(ccRCC)
is
a
common
clinical
tumor
of
the
urinary
system.
The
lack
effective
diagnostic
and
treatment
options
poses
serious
challenge
to
treatment.
Therefore,
identifying
molecular
targets
has
become
one
potential
means
treat
this
disease.
Firstly,
analysis
TCGA
database
found
that
PLAC1
was
abnormally
highly
expressed
in
ccRCC
negatively
correlated
with
patient
prognosis.
Western
blotting
immunofluorescence
experiments
further
verified
patients,
knockdown
inhibited
development
vitro.
Last,
high-throughput
virtual
screening
technology
(HTVS)
performed
identify
two
inhibitors
，AmB
Cana,
which
were
able
reduce
expression
progression
ccRCC.
In
conclusion,
current
investigation
indicated
could
serve
as
prognostic
biomarker,
AmB
Cana
inhibit
by
reducing
PLAC1,
making
it
therapeutic
option
for
Abstract
Accurately
defining
cell
boundaries
for
spatial
transcriptomics
is
technically
challenging.
The
current
major
approaches
are
nuclear
staining
or
mathematical
inference,
which
either
exclude
the
cytoplasm
determine
a
hypothetical
boundary.
Here,
new
method
introduced
boundaries:
labeling
membranes
using
genetically
coded
fluorescent
proteins,
allows
precise
indexing
of
sequencing
spots
and
transcripts
within
cells
on
sections.
Use
this
membrane‐based
greatly
increases
number
genes
captured
in
compared
to
nucleus‐based
methods;
numbers
increased
by
67%
119%
mouse
axolotl
livers,
respectively.
obtained
expression
profiles
more
consistent
with
single‐cell
RNA‐seq
data,
demonstrating
rational
clustering
apparent
type‐specific
markers.
Furthermore,
improved
resolution
achieved
better
identify
rare
types
elaborate
domains
brain
intestine.
In
addition
regular
cells,
accurate
recognition
multinucleated
lacking
nuclei
liver
achieved,
its
ability
analyze
complex
tissues
organs,
not
achievable
previous
methods.
This
study
provides
powerful
tool
improving
that
has
broad
potential
applications
biological
medical
sciences.
Frontiers in Immunology,
Год журнала:
2025,
Номер
15
Опубликована: Янв. 6, 2025
The
Aryl
Hydrocarbon
Receptor
(AhR)
pathway
significantly
influences
immune
cell
regulation,
impacting
the
effectiveness
of
immunotherapy
and
patient
outcomes
in
melanoma.
However,
specific
downstream
targets
mechanisms
by
which
AhR
melanoma
remain
insufficiently
understood.
Melanoma
samples
from
Cancer
Genome
Atlas
(TCGA)
normal
skin
tissues
Genotype-Tissue
Expression
(GTEx)
database
were
analyzed
to
identify
differentially
expressed
genes,
intersected
with
a
curated
list
AhR-related
genes.
Prognostic
models
subsequently
developed,
feature
genes
identified.
Advanced
methodologies,
including
Gene
Set
Enrichment
Analysis
(GSEA)
infiltration
analysis,
employed
explore
biological
significance
these
stability
machine
learning
relationship
between
gene
expression
infiltrating
cells
validated
using
three
independent
datasets.
A
mouse
model
was
used
validate
dynamic
changes
during
tumor
progression.
selected
drug
sensitivity,
as
well
non-coding
RNA
interactions,
thoroughly
investigated.
Our
analysis
identified
robust
prognostic
model,
four
(MAP2K1,
PRKACB,
KLF5,
PIK3R2)
emerging
key
contributors
GSEA
revealed
that
are
involved
primary
immunodeficiency.
Immune
demonstrated
enrichment
CD4+
naïve
memory
T
cells,
macrophages
(M0
M2),
CD8+
melanoma,
all
associated
Importantly,
diagnostic
power
relevance
additional
In
Map2k1
Prkacb
mRNA
levels
exhibited
progressive
increase
progression,
supporting
their
role
advancement.
This
study
presents
comprehensive
highlighting
MAP2K1,
PIK3R2
markers
potential
therapeutic
targets.
integration
bioinformatics
provides
framework
for
enhancing
evaluation
patients
offers
new
avenues
development
treatments,
particularly
those
resistant
current
immunotherapies.
Journal of Translational Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Янв. 27, 2025
Tumor-associated
fibrosis
modifies
the
tumor
microenvironment
(TME),
hinders
infiltration
and
activity
of
cytotoxic
immune
cells,
is
a
critical
pathological
process
leading
to
ineffectiveness
immunotherapy
in
gastric
cancer
(GC).
However,
specific
mechanisms
interventions
are
yet
be
fully
explored.
Our
study
included
375
samples
from
TCGA,
1
single-cell
RNA
sequencing
(scRNA-seq)
dataset
comprising
15
GEO,
19
cohorts
2
GWAS
datasets.
Consensus
clustering
identified
subtype
characterized
primarily
by
fibrosis,
various
methods
such
as
pseudotime
analysis,
CellChat
analysis
Colocalization
were
used
explore
its
mechanisms.
A
was
with
poor
prognosis,
higher
malignancy,
drug
resistance,
infiltration,
associated
elevated
expression
genes
related
Extracellular
matrix
(ECM).
Single-cell
transcriptome
showed
active
Collagen-CD44
signaling
axis
between
cancer-associated
fibroblasts
(CAFs)
cells
cancer,
ECM-related
upregulated
during
progression.
The
CD44
significantly
subtype,
prognosis
suppression
potentially
involved
recruitment
immunosuppressive
M2
macrophages
regulatory
T
(Tregs)
upregulation
multiple
checkpoints
including
PD-1/PD-L1.
new
revealing
that
mechanism
driving
emphasizing
central
role
axis.
has
potential
serve
novel
therapeutic
target
for
enhancing
cell-mediated
suppression.
By
combining
it
checkpoint
inhibitors
(ICIs),
may
improve
efficacy
offer
hope
treatment.
Frontiers in Immunology,
Год журнала:
2025,
Номер
16
Опубликована: Март 7, 2025
Background
Gastric
cancer
(GC)
remains
a
leading
cause
of
cancer-related
mortality,
with
over
one
million
new
cases
and
769,000
deaths
reported
in
2020.
Despite
advancements
chemotherapy,
surgery,
targeted
therapies,
delayed
diagnosis
due
to
overlooked
early
symptoms
leads
poor
prognosis.
Methods
We
integrated
bulk
RNA
sequencing
single-cell
datasets
from
TCGA,
GEO,
OMIX001073,
employing
normalization,
batch
effect
correction,
dimensionality
reduction
methods
identify
key
cell
populations
associated
GC
invasion
epithelial-mesenchymal
transition
(EMT),
as
well
analyze
the
tumor
immune
microenvironment.
Results
Our
analysis
identified
MUC5AC+
malignant
epithelial
cluster
significant
player
EMT.
Cluster
1,
representing
this
population,
exhibited
higher
EMT
scores
compared
other
clusters.
Survival
showed
that
high
abundance
0
correlated
improved
survival
rates
(P=0.012),
whereas
1
was
poorer
outcomes
(P=0.045).
A
prognostic
model
highlighted
ANXA5
GABARAPL2
two
critical
genes
upregulated
tumors.
High-risk
patients
demonstrated
increased
infiltration
worse
prognosic.
Analysis
mutation
burden
(TMB)
indicated
low
TMB
high-risk
group
had
worst
Wet-lab
validation
experiments
confirmed
oncogenic
role
ANXA5,
showing
its
facilitation
proliferation,
invasion,
migration
while
suppressing
apoptosis.
Conclusion
This
study
offers
novel
insights
into
subpopulations
cells
their
roles
progression.
It
provides
potential
therapeutic
targets
combat
GC,
contributing
crucial
understanding
fundamental
mechanisms
drug
resistance
gastrointestinal
cancers.
