Cell Reports Medicine,
Journal Year:
2021,
Volume and Issue:
2(12), P. 100472 - 100472
Published: Dec. 1, 2021
Understanding
the
molecular
determinants
that
underpin
clinical
heterogeneity
of
non-muscle-invasive
bladder
cancer
(NMIBC)
is
essential
for
prognostication
and
therapy
development.
Stage
T1
disease
in
particular
presents
a
high
risk
progression
requires
improved
understanding.
We
present
detailed
multi-omics
study
containing
gene
expression,
copy
number,
mutational
profiles
show
relationships
to
immune
infiltration,
recurrence,
muscle
invasion.
compare
expression
genomic
subtypes
derived
from
all
NMIBCs
with
those
individual
stages
Ta
T1.
sufficient
exists
within
separate
allow
subclassification
this
more
clinically
meaningful
stage
than
NMIBCs.
This
provides
biological
understanding
identifies
tumors
may
benefit
chemo-
or
immunotherapy.
European Urology,
Journal Year:
2019,
Volume and Issue:
77(4), P. 420 - 433
Published: Sept. 26, 2019
Muscle-invasive
bladder
cancer
(MIBC)
is
a
molecularly
diverse
disease
with
heterogeneous
clinical
outcomes.
Several
molecular
classifications
have
been
proposed,
but
the
diversity
of
their
subtype
sets
impedes
application.
To
achieve
an
international
consensus
on
MIBC
subtypes
that
reconciles
published
classification
schemes.
We
used
1750
transcriptomic
profiles
from
16
datasets
and
two
additional
cohorts.
performed
network-based
analysis
six
independent
systems
to
identify
set
classes.
Association
survival
was
assessed
using
multivariable
Cox
models.
report
results
effort
reach
subtypes.
identified
classes:
luminal
papillary
(24%),
nonspecified
(8%),
unstable
(15%),
stroma-rich
basal/squamous
(35%),
neuroendocrine-like
(3%).
These
classes
differ
regarding
underlying
oncogenic
mechanisms,
infiltration
by
immune
stromal
cells,
histological
characteristics,
including
provide
single-sample
classifier
assigns
class
label
tumor
sample's
transcriptome.
Limitations
work
are
retrospective
data
collection
lack
complete
information
patient
treatment.
This
system
offers
robust
framework
will
enable
testing
validation
predictive
biomarkers
in
future
prospective
trials.
Bladder
cancers
at
level,
scientists
proposed
several
into
While
these
may
be
useful
stratify
patients
for
prognosis
or
response
treatment,
would
facilitate
use
Conducted
multidisciplinary
expert
teams
field,
this
study
proposes
such
provides
tool
applying
setting.
Nature Communications,
Journal Year:
2021,
Volume and Issue:
12(1)
Published: April 16, 2021
Abstract
The
molecular
landscape
in
non-muscle-invasive
bladder
cancer
(NMIBC)
is
characterized
by
large
biological
heterogeneity
with
variable
clinical
outcomes.
Here,
we
perform
an
integrative
multi-omics
analysis
of
patients
diagnosed
NMIBC
(
n
=
834).
Transcriptomic
identifies
four
classes
(1,
2a,
2b
and
3)
reflecting
tumor
biology
disease
aggressiveness.
Both
transcriptome-based
subtyping
the
level
chromosomal
instability
provide
independent
prognostic
value
beyond
established
clinicopathological
parameters.
High
instability,
p53-pathway
disruption
APOBEC-related
mutations
are
significantly
associated
transcriptomic
class
2a
poor
outcome.
RNA-derived
immune
cell
infiltration
chromosomally
unstable
tumors
enriched
2b.
Spatial
proteomics
confirms
higher
demonstrates
association
between
lower
recurrence
rates.
Finally,
documented
1228
validation
samples
using
a
single
sample
classification
tool.
classifier
provides
framework
for
biomarker
discovery
optimizing
treatment
surveillance
next-generation
trials.
Nature Communications,
Journal Year:
2019,
Volume and Issue:
10(1)
Published: July 5, 2019
Upper
tract
urothelial
carcinoma
(UTUC)
is
characterized
by
a
distinctly
aggressive
clinical
phenotype.
To
define
the
biological
features
driving
this
phenotype,
we
performed
an
integrated
analysis
of
whole-exome
and
RNA
sequencing
UTUC.
Here
report
several
key
insights
from
our
molecular
dissection
disease:
1)
Most
UTUCs
are
luminal-papillary;
2)
UTUC
has
T-cell
depleted
immune
contexture;
3)
High
FGFR3
expression
enriched
in
correlates
with
its
microenvironment;
4)
Sporadic
lower
total
mutational
burden
than
bladder.
Our
findings
lay
foundation
for
deeper
understanding
biology
provide
rationale
development
UTUC-specific
treatment
strategies.
European Urology,
Journal Year:
2021,
Volume and Issue:
81(5), P. 523 - 532
Published: Nov. 14, 2021
For
muscle-invasive
bladder
cancer
(MIBC),
no
tissue
biomarkers
are
available
for
clinical
use
to
predict
response
neoadjuvant
chemotherapy.To
investigate
how
molecular
subtypes
impact
pathological
and
survival
in
patients
receiving
preoperative
cisplatin-based
chemotherapy.Classification
of
a
retrospective
cohort
149
was
performed
by
tumor
transcriptomic
profiling
immunostaining.
A
treated
with
radical
cystectomy
alone
public
data
sets
were
used
comparison
external
validation.Complete
the
specimen
(ypT0N0)
compared
predefined
subtypes.
Differential
gene
expression
chemotherapy
explored
beyond
subtypes.Patients
genomically
unstable
(GU)
urothelial-like
(Uro)
tumors
had
higher
proportions
complete
(16/31
[52%]
17/54
[31%]),
versus
five
out
24
(21%)
basal/squamous
(Ba/Sq)
subtype
following
cystectomy.
Molecular
independently
associated
improved
GU
(hazard
ratio
[HR]
0.29,
95%
confidence
interval
[CI]:
0.11-0.79)
UroC
(HR
0.37,
CI:
0.14-0.94)
Ba/Sq
tumors,
adjusting
stage.
In
addition,
coding
osteopontin
(SPP1)
showed
subtype-dependent
effect
on
response.Urothelial
luminal-like
(GU
Uro)
is
more
responsive
chemotherapy.
second-generation
subtype-specific
biomarkers,
example,
SPP1,
may
be
way
forward
develop
precision-based
treatment
approach
MIBC.This
study
shows
that
classification
subtyping
can
identify
who
likely
benefit
from
before
cancer.
Together
other
markers
response,
could
have
role
selective
administration
such
