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Evaluation of a 4-protein serum biomarker panel-biglycan, annexin-A6, myeloperoxidase, and protein S100-A9 (B-AMP)-for the detection of esophageal adenocarcinoma.
[esophageal adenocarcinoma]
Esophageal
adenocarcinoma
(
EAC
)
is
associated
with
a
dismal
prognosis
.
The
identification
of
cancer
biomarkers
can
advance
the
possibility
for
early
detection
and
better
monitoring
of
tumor
progression
and
/
or
response
to
therapy
.
The
authors
present
results
from
the
development
of
a
serum-based
,
4
-
protein
(
biglycan
,
myeloperoxidase
,
annexin-
A
6
,
and
protein
S
100
-
A
9
)
biomarker
panel
for
EAC
.
A
vertically
integrated
,
proteomics-based
biomarker
discovery
approach
was
used
to
identify
candidate
serum
biomarkers
for
the
detection
of
EAC
.
Liquid
chromatography-tandem
mass
spectrometry
analysis
was
performed
on
formalin-fixed
,
paraffin-embedded
tissue
samples
that
were
collected
from
across
the
Barrett
esophagus
(
BE
)
-
EAC
disease
spectrum
.
The
mass
spectrometry-based
spectral
count
data
were
used
to
guide
the
selection
of
candidate
serum
biomarkers
.
Then
,
the
serum
enzyme-linked
immunosorbent
assay
data
were
validated
in
an
independent
cohort
and
were
used
to
develop
a
multiparametric
risk-assessment
model
to
predict
the
presence
of
disease
.
With
a
minimum
threshold
of
10
spectral
counts
,
351
proteins
were
identified
as
differentially
abundant
along
the
spectrum
of
Barrett
esophagus
,
high
-grade
dysplasia
,
and
EAC
(
P
<
.
05
)
.
Eleven
proteins
from
this
data
set
were
then
tested
using
enzyme-linked
immunosorbent
assays
in
serum
samples
,
of
which
5
proteins
were
significantly
elevated
in
abundance
among
patients
who
had
EAC
compared
with
normal
controls
,
which
mirrored
trends
across
the
disease
spectrum
present
in
the
tissue
data
.
By
using
serum
data
,
a
Bayesian
rule-learning
predictive
model
with
4
biomarkers
was
developed
to
accurately
classify
disease
class
;
the
cross-validation
results
for
the
merged
data
set
yielded
accuracy
of
87
%
and
an
area
under
the
receiver
operating
characteristic
curve
of
93
%
.
Serum
biomarkers
hold
significant
promise
for
the
early
,
noninvasive
detection
of
EAC
.
Cancer
2014
.
©
2014
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