Background
Methods
Patients
DNA extraction and bisulfite modification
Statistical analysis
Results
Demographic and clinicopathological data
No. | Average | SD |
P-value | |
---|---|---|---|---|
Sex | ||||
M | 121 | 75.48 | 7.173 | 0.233 |
F | 51 | 76.97 | 8.216 | |
Age | ||||
<64 years | 87 | 75.97 | 8.274 | 0.936 |
≥64 years | 85 | 75.87 | 6.674 | |
Gross type | ||||
Mass forming | 141 | 75.66 | 7.616 | 0.702 (ANOVA) |
Periductal infiltrative | 8 | 78.62 | 3.790 | 0.558 (KW) |
Intraductal growth | 18 | 76.73 | 7.110 | |
Mixed | 5 | 76.16 | 10.837 | |
Multiplicity | ||||
single | 147 | 75.73 | 7.898 | 0.422 |
multiple | 25 | 77.04 | 4.501 | |
T stage | ||||
pT1 | 48 | 78.08 | 6.972 | 0.049 (ANOVA) |
pT2a | 38 | 73.08 | 9.417 | 0.012 (KW) |
pT2b | 14 | 76.12 | 4.010 | |
pT3 | 47 | 76.04 | 7.026 | |
pT4 | 25 | 75.74 | 6.622 | |
N stage | ||||
pN0 | 133 | 75.96 | 7.861 | 0.899 |
pN1 | 39 | 75.78 | 6.223 | |
M stage | ||||
pM0 | 161 | 76.17 | 7.593 | 0.095 |
pM1 | 11 | 72.26 | 4.972 | 0.035 (MWa) |
TNM stage | ||||
I | 40 | 77.81 | 7.579 | 0.229 |
II | 37 | 74.42 | 8.747 | |
III | 30 | 76.25 | 7.801 | |
IV | 65 | 75.45 | 6.406 | |
Differentiation | ||||
Well | 23 | 79.69 | 4.766 | 0.014 |
Moderate | 94 | 75.95 | 6.857 | |
Poorly | 55 | 74.28 | 8.906 | |
Neural invasion | ||||
Absent | 118 | 75.77 | 8.146 | 0.701 |
Present | 54 | 76.25 | 5.921 | |
Lymphatic invasion | ||||
Absent | 102 | 76.92 | 7.200 | 0.034 |
Present | 70 | 74.46 | 7.749 | |
Vascular invasion | ||||
Absent | 95 | 76.44 | 8.141 | 0.396 |
Present | 77 | 75.27 | 6.631 | 0.047 (MWa) |
Chronic liver disease | ||||
Absent | 130 | 75.95 | 7.497 | 0.936 |
Present | 42 | 75.84 | 7.617 | |
Chronic biliary disease | ||||
Absent | 159 | 75.93 | 7.679 | 0.962 |
Present | 13 | 75.82 | 5.108 |
Relationship between LINE-1 methylation level and clinicopathological features
Relationship between tumoral LINE-1 methylation status and cancer-specific survival of patients with ICC
Parameters | Hazard ratio (95% C.I.) |
P-value | |
---|---|---|---|
LINE-1 methylation status | 0.017 | ||
Q4 (n = 43) | Reference | ||
Q3 (n = 43) | 1.575 (0.561–4.602) | 0.320 | |
Q2 (n = 43) | 3.369 (1.328–8.551) | 0.011 | |
Q1 (n = 43) | 3.400 (1.349–8.570) | 0.009 | |
LINE-1 methylation status | Q3, Q4 (n = 86) | ||
Q1, Q2 (n = 86) | 2.643 (1.443–4.482) | 0.002 | |
pTNM staging | 0.145 | ||
I (n = 43) | Reference | ||
II (n = 38) | 1.636 (0.739–3.622) | 0.224 | |
III (n = 30) | 0.543 (0.173–1.709) | 0.297 | |
IV (n = 61) | 1.602 (0.768–3.342) | 0.209 | |
T staging | 0.044 | ||
pT1 (n = 48) | Reference | ||
pT2a (n = 38) | 1.809 (0.866–3.777) | 0.114 | |
pT2b (n = 14) | 2.344 (0.929–5.913) | 0.071 | |
pT3 (n = 47) | 0.941 (0.420–2.107) | 0.883 | |
pT4 (n = 25) | 0.433 (0.123–1.524) | 0.192 | |
N staging | pN0 (n = 133) | ||
pN1 (n = 39) | 2.328 (1.304–4.157) | 0.004 | |
M staging | pM0 (n = 161) | ||
pM1 (n = 11) | 1.482 (0.533–4.118) | 0.451 | |
Gross type | 0.076 | ||
Mass forming (n = 141) | Reference | ||
Periductal infiltrative (n = 8) | 0 | 0.964 | |
Intraductal growth (n = 18) | 0.134 (0.018–0.971) | 0.047 | |
Mixed (n = 5) | 2.672 (0.827–8.638) | 0.101 | |
Lymphatic emboli | Absent (n = 102) | ||
Present (n = 70) | 2.519 (1.429–4.438) | 0.001 | |
Vascular invasion | Absent (n = 95) | ||
Present (n = 77) | 1.111 (0.634–1.945) | 0.714 | |
Perineural invasion | Absent (n = 118) | ||
Present (n = 54) | 0.386 (0.181–0.822) | 0.014 | |
Tumor border | Expanding (n = 32) | ||
Infiltrative (n = 140) | 2.133 (0.846–5.375) | 0.108 | |
Tumor differentiation | 0.083 | ||
Well (n = 23) | Reference | ||
Moderate (n = 94) | 9.405 (1.283–68.943) | 0.027 | |
Poor (n = 55) | 9.671 (1.290–72.518) | 0.027 | |
Chemotherapy and/or radiotherapy | No (n = 120) | ||
Yes (n = 52) | 0.979 (0.534–1.792) | 0.944 |
Hazard ratio (95% C.I.) |
P-value | Hazard ratio (95% C.I.) |
P-value | ||
---|---|---|---|---|---|
LINE-1 methylation levela
| Q3, Q4 (n = 86) | ||||
Q1, Q2 (n = 86) | 2.643 (1.443–4.482) | 0.002 | 2.248 (1.205–4.196) | 0.011 | |
N staging | pN0 (n = 133) | ||||
pN1 (n = 39) | 2.211 (1.176–4.157) | 0.014 | 2.749 (1.491–5.066) | 0.001 | |
T staging | 0.025 | 0.130 | |||
pT1 (n = 48) | Reference | Reference | |||
pT2 (n = 52) | 1.943 (0.979–3.855) | 0.058 | 0.555 (0.211–1.458) | 0.232 | |
pT3 (n = 47) | 0.941 (0.420–2.105) | 0.882 | 0.363 (0.121–1.091) | 0.071 | |
pT4 (n = 25) | 0.433 (0.123–1.523) | 0.192 | 0.216 (0.053–0.889) | 0.034 | |
Gross type | 0.076 | 0.064 | |||
Mass forming (n = 141) | Reference | Reference | |||
Periductal infiltrative (n = 8) | 0 | 0.964 | 0 | 0.972 | |
Intraductal growth (n = 18) | 0.134 (0.018–0.971) | 0.047 | 0.123 (0.017–0.910) | 0.040 | |
Mixed (n = 5) | 2.672 (0.827–8.638) | 0.101 | 2.878 (0.854–9.694) | 0.088 | |
Lymphatic emboli | Absent (n = 102) | ||||
Present (n = 70) | 2.519 (1.429–4.438) | 0.001 | 2.720 (1.168–6.337) | 0.020 | |
Perineural invasion | Absent (n = 118) | ||||
Present (n = 54) | 0.386 (0.181–0.822) | 0.014 | 0.373 (0.162–0.860) | 0.021 | |
Differentiation | 0.083 | 0.638 | |||
Well (n = 23) | Reference | ||||
Moderate (n = 94) | 9.405 (1.283–68.943) | 0.027 | |||
Poor (n = 55) | 9.671 (1.290–72.518) | 0.027 |
Discussion
Parameters | Hazard ratio (95% C.I.) |
P-value | |
---|---|---|---|
LINE-1 methylation /lymphatic emboli status | 0.001 | ||
High/absent (n = 58) | Reference | ||
Low/present (n = 28) | 3.128 (1.523–6.424) | 0.002 | |
Low/absent (n = 44) | 1.113 (0.460–2.695) | 0.812 | |
High/present (n = 42) | 0.761 (0.237–2.443) | 0.647 | |
Gross type | 0.073 | ||
Mass forming (n = 141) | Reference | ||
Periductal infiltrative (n = 8) | 0 | 0.972 | |
Intraductal growth (n = 18) | 0.141 (0.019–1.032) | 0.054 | |
Mixed (n = 5) | 3.013 (0.885–10.254) | 0.078 | |
T staging | 0.152 | ||
pT1 (n = 48) | Reference | ||
pT2 (n = 52) | 0.579 (0. 220–1.526) | 0.270 | |
pT3 (n = 47) | 0.371 (0.124–1.114) | 0.077 | |
pT4 (n = 25) | 0.233 (0.056–0.971) | 0.046 | |
N staging | pN0 (n = 133) | ||
pN1 (n = 39) | 2.456 (1.341–4.497) | 0.004 | |
Perineural invasion | Absent (n = 118) | ||
Present (n = 54) | 0.321 (0.147–0.699) | 0.004 | |
Differentiation | 0.577 | ||
Well (n = 23) | Reference | ||
Moderate (n = 94) | 3.495 (0.332–36.809) | 0.298 | |
Poor (n = 55) | 3.493 (0.328–37.217) | 0.300 |