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LINE-1 Methylation Level and Patient Prognosis in a Database of 208 Hepatocellular Carcinomas.
[esophageal squamous cell carcinoma]
The
level
of
long
interspersed
nucleotide
element-
1
(
LINE-
1
)
methylation
has
become
regarded
as
a
surrogate
marker
of
global
DNA
methylation
.
Previously
,
we
demonstrated
that
LINE-
1
hypomethylation
might
contribute
to
the
acquisition
of
aggressive
tumor
behavior
through
genomic
gains
of
oncogenes
such
as
cyclin-dependent
kinase
6
(
CDK
6
)
in
esophageal
squamous
cell
carcinoma
.
However
,
the
relationship
between
LINE-
1
hypomethylation
and
clinical
outcome
in
hepatocellular
carcinoma
(
HCC
)
remains
unclear
.
L
INE-
1
methylation
level
in
208
samples
of
curatively
resected
HCCs
was
measured
by
pyrosequencing
assay
,
and
the
prognostic
value
of
LINE-
1
methylation
level
in
HCC
was
examined
.
L
INE-
1
methylation
levels
in
the
208
HCC
patients
investigated
were
distributed
as
follows
:
mean
64
.
7
;
median
64
.
6
;
standard
deviation
(
SD
)
13
.
6
;
range
21
.
5
-
99
.
1
;
interquartile
range
62
.
9
-
66
.
6
.
Univariate
Cox
regression
analysis
revealed
a
significantly
higher
cancer
recurrence
rate
in
the
low
-methylation-level
group
than
in
the
high
-methylation-level
group
(
hazard
ratio
1
.
58
;
95
Â
%
CI
1
.
05
-
2
.
47
;
p
Â
=
Â
0
.
028
)
.
Interestingly
,
the
influence
of
LINE-
1
hypomethylation
on
patient
outcome
was
modified
by
hepatitis
virus
infection
(
p
of
interaction
Â
=
Â
0
.
023
)
;
LINE-
1
hypomethylation
was
associated
with
a
higher
cancer
recurrence
rate
in
patients
without
hepatitis
virus
infection
(
log-rank
p
Â
=
Â
0
.
0047
)
.
CDK
6
messenger
RNA
expression
levels
were
inversely
associated
with
LINE-
1
methylation
levels
(
p
Â
=
Â
0
.
0075
;
R
Â
=
Â
-
0
.
37
)
.
Genome-
wide
DNA
hypomethylation
,
as
measured
by
LINE-
1
levels
,
might
be
associated
with
poor
disease-free
survival
in
HCC
patients
,
suggesting
a
potential
role
for
LINE-
1
methylation
level
as
a
biomarker
for
identifying
patients
who
will
experience
an
unfavorable
clinical
outcome
.
Diseases
Validation
Diseases presenting
"interspersed nucleotide element-1"
symptom
esophageal squamous cell carcinoma
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