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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
"squamous cell carcinoma"
symptom
carcinoma of the gallbladder
child syndrome
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
esophageal adenocarcinoma
esophageal carcinoma
esophageal squamous cell carcinoma
junctional epidermolysis bullosa
kallmann syndrome
kindler syndrome
liposarcoma
monosomy 21
oculocutaneous albinism
oral submucous fibrosis
papillon-lefèvre syndrome
This symptom has already been validated