One-carbon metabolic reprogramming and its relationship with tumor-infiltrating lymphocytes and Immune checkpoint in Pancreatic cancer
Abstract
BACKGROUND
The
role
of
oncogene-driven
metabolic
reprogramming
in
pancreatic
cancer
(PC)
remains
unclear.
This
study
explored
the
interplay
between
one-carbon
metabolism
(OCM),
driver
genes,
and
tumor
microenvironment
(TME)
PC.
METHODS
Targeted
metabolomics
analyzed
136
PC
serum
samples.
Transcriptomic
OCM
gene
data
from
930
patients
were
obtained
public
databases.
Non-negative
matrix
factorization
(NMF)
clustering
classified
subtypes.
Single-cell
analysis
deciphered
features
TME.
Immunohistochemistry
assessed
MTHFD1L
expression,
cancer-associated
fibroblast
(CAF)
markers
(FAP,
α-SMA),
immune
cells
(CD8+/Foxp3+
TILs,
CD206+
TAMs),
PD-1/PD-L1
138
tissue
RESULTS
identified
altered
amino
acid
(73
metabolites).
NMF
stratified
into
C1/C2
subtypes
with
distinct
prognoses
TME
characteristics
(p<0.05).
revealed
dysregulation
cells,
macrophages,
fibroblasts.
emerged
as
a
core
reprogramming,
correlating
poor
overall
survival
(OS,
p=0.005)
disease-free
(DFS,
p=0.006).
High
expression
was
linked
to
lymph
node
metastasis
positively
associated
FAP
CAFs
(p<0.05),
TAMs
(p<0.001),
Foxp3+
TIL
infiltration
Multivariate
confirmed
an
independent
prognostic
factor
(p=0.022).
CONCLUSION
OCM
is
hallmark
drives
oncogenic
influences
prognosis
by
modulating
CAFs,
TAMs,
Tregs.
Targeting
or
may
offer
therapeutic
potential.
Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown
Published: May 7, 2025
Language: Английский