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A validated miRNA profile predicts response to therapy in esophageal adenocarcinoma.
[esophageal adenocarcinoma]
In
the
current
study
we
present
a
validated
miRNA
signature
to
predict
pathologic
complete
response
(
pCR
)
to
neoadjuvant
chemoradiation
in
esophageal
adenocarcinoma
.
Three
patient
cohorts
(
discovery
,
n
 
=
 
10
;
model
,
n
 
=
 
43
;
and
validation
,
n
 
=
 
65
)
with
locally
advanced
esophageal
adenocarcinoma
were
analyzed
.
In
the
discovery
cohort
754
miRNAs
were
examined
in
pretreatment
tumor
biopsy
specimens
using
a
TaqMan
array
.
Of
these
,
the
44
most
significantly
altered
between
tumors
with
pCR
and
non-p
CR
were
examined
in
an
additional
43
tumors
using
a
Fluidigm
48
.
48
array
.
The
4
miRNAs
(
mir-
505
*
,
mir-
99
b
,
mir-
451
,
and
mir-
145
*
)
significantly
predicting
pCR
in
both
cohorts
were
examined
in
an
additional
validation
cohort
(
n
 
=
 
65
)
using
an
Illumina
array
.
These
4
miRNAs
were
used
to
generate
an
miRNA
expression
profile
(
MEP
)
score
.
The
4
miRNAs
profiled
are
highly
significantly
associated
with
pCR
in
the
model
cohort
(
Ptrend
 
=
 
.
008
)
,
the
validation
cohort
(
Ptrend
 
=
 
.
025
)
,
and
the
combined
cohort
(
Ptrend
 
=
 
4
.
6
×
10
(
-
4
)
)
.
The
receiver-operator
characteristic
areas
under
the
curves
(
AUCs
)
for
the
MEP
score
were
0
.
78
for
the
model
cohort
,
0
.
71
for
the
validation
cohort
,
and
0
.
72
for
the
combined
cohort
.
When
combined
with
clinical
variables
,
the
MEP
score
AUCs
increased
to
0
.
89
,
0
.
77
,
and
0
.
81
,
respectively
Estimates
from
logistic
regression
based
on
the
MEP
were
determined
and
used
to
generate
a
probability
of
pCR
plot
,
which
identifies
a
group
of
patients
with
very
high
(
≥
80
%
)
and
very
low
(
≤
10
%
)
probability
of
pCR
.
The
MEP
score
provides
a
validated
means
of
predicting
pCR
to
neoadjuvant
chemoradiotherapy
in
esophageal
adenocarcinoma
that
is
robust
across
several
analysis
platforms
.
Cancer
2014
;
120
:
3635
-
3641
.
©
2014
The
Authors
.
Cancer
published
by
Wiley
Periodicals
,
Inc
.
on
behalf
of
American
Cancer
Society
.
Diseases
Validation
Diseases presenting
"cancer"
symptom
achondroplasia
acute rheumatic fever
adrenal incidentaloma
alpha-thalassemia
benign recurrent intrahepatic cholestasis
cadasil
canavan disease
carcinoma of the gallbladder
cholangiocarcinoma
coats disease
congenital adrenal hyperplasia
congenital diaphragmatic hernia
cowden syndrome
cushing syndrome
cutaneous mastocytosis
dedifferentiated liposarcoma
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
erdheim-chester disease
erythropoietic protoporphyria
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
familial hypocalciuric hypercalcemia
familial mediterranean fever
gm1 gangliosidosis
heparin-induced thrombocytopenia
hereditary cerebral hemorrhage with amyloidosis
hirschsprung disease
hodgkin lymphoma, classical
inclusion body myositis
junctional epidermolysis bullosa
kabuki syndrome
kallmann syndrome
kindler syndrome
lamellar ichthyosis
liposarcoma
locked-in syndrome
lymphangioleiomyomatosis
monosomy 21
neuralgic amyotrophy
oculocutaneous albinism
oligodontia
oral submucous fibrosis
papillon-lefèvre syndrome
pendred syndrome
pleomorphic liposarcoma
primary effusion lymphoma
proteus syndrome
pyomyositis
pyruvate dehydrogenase deficiency
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
von hippel-lindau disease
waldenström macroglobulinemia
well-differentiated liposarcoma
werner syndrome
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
This symptom has already been validated