Fig. 1Immunostaining of BCL9 showing nuclear expression in hepatocellular carcinoma (A) and no nuclear expression in dysplastic nodule (B) (horseradish peroxidase stain).
Fig. 2Kaplan-Meier survival curves showing disease-free survival (A) and disease-specific survival (B) for BCL9 expression in 288 hepatocellular carcinomas.
Table 1.Correlation of BCL9 expression and tumor recurrence with clinicopathologic features in 288 hepatocellular carcinomas
Variable |
n |
Tumor recurrence |
p-value |
BCL9 expression |
p-value |
Age (yr) |
|
|
0.151 |
|
0.038 |
≤ 55 |
165 |
114 (69.1) |
|
50 (30.3) |
|
> 55 |
123 |
75 (61.0) |
|
24 (19.5) |
|
Gender |
|
|
0.619 |
|
0.457 |
Male |
237 |
154 (65.0) |
|
63 (26.6) |
|
Female |
51 |
35 (68.6) |
|
11 (21.6) |
|
Tumor size (cm) |
|
|
0.011 |
|
0.816 |
≤ 5.0 |
190 |
115 (60.5) |
|
48 (25.3) |
|
> 5.0 |
98 |
74 (75.5) |
|
26 (26.5) |
|
Edmondson grade |
|
|
0.029 |
|
0.001 |
I |
30 |
20 (66.7) |
|
3 (10.0) |
|
II |
195 |
119 (61.0) |
|
44 (22.6) |
|
III |
63 |
50 (79.4) |
|
27 (42.9) |
|
Microvascular invasion |
|
|
0.001 |
|
0.013 |
(-) |
129 |
71 (55.0) |
|
24 (18.6) |
|
(+) |
159 |
118 (74.2) |
|
50 (31.4) |
|
Major portal vein invasion |
|
|
0.038 |
|
0.084 |
(-) |
275 |
177 (64.4) |
|
68 (24.7) |
|
(+) |
13 |
12 (92.3) |
|
6 (46.2) |
|
Intrahepatic metastasis |
|
|
< 0.001 |
|
0.017 |
(-) |
220 |
127 (57.7) |
|
49 (22.3) |
|
(+) |
68 |
62 (91.2) |
|
24 (36.8) |
|
Multicentric occurrence |
|
|
0.815 |
|
0.419 |
(-) |
269 |
177 (65.8) |
|
71 (26.4) |
|
(+) |
19 |
12 (63.2) |
|
3 (15.8) |
|
AJCC T stage |
|
|
< 0.001 |
|
0.098 |
1 |
121 |
67 (55.4) |
|
23 (19.0) |
|
2 |
117 |
76 (65.0) |
|
34 (29.1) |
|
3 |
44 |
41 (93.2) |
|
14 (31.8) |
|
4 |
6 |
5 (83.3) |
|
3 (50.0) |
|
BCLC stage |
|
|
0.004 |
|
0.378 |
0-A |
164 |
95 (57.9) |
|
39 (23.8) |
|
B |
109 |
81 (74.3) |
|
29 (26.6) |
|
C |
15 |
13 (86.7) |
|
6 (40.0) |
|
Albumin level (g/dL) |
|
|
0.179 |
|
0.312 |
> 3.5 |
258 |
166 (64.3) |
|
64 (24.8) |
|
≤ 3.5 |
30 |
23 (76.7) |
|
10 (33.3) |
|
AFP level (ng/mL) |
|
|
0.002 |
|
0.091 |
≤ 200 |
173 |
102 (59.0) |
|
39 (22.5) |
|
> 200 |
104 |
80 (76.9) |
|
33 (31.7) |
|
Etiology |
|
|
0.004 |
|
0.391 |
Non-viral |
40 |
17 (42.5) |
|
7 (17.5) |
|
HBV |
218 |
150 (68.8) |
|
60 (27.5) |
|
HCV |
30 |
22 (73.3) |
|
7 (25.7) |
|
Liver cirrhosis |
|
|
0.009 |
|
0.590 |
(-) |
144 |
84 (58.3) |
|
35 (24.3) |
|
(+) |
144 |
105 (72.9) |
|
39 (27.1) |
|
Table 2.Univariate analyses of disease-free survival and disease-specific survival in 288 hepatocellular carcinomas
Variable |
|
n |
Disease-free survival
|
Disease-specific survival
|
|
HR (95% CI) |
p-value |
HR (95% CI) |
p-value |
Tumor size (cm) |
≤ 5.0 |
190 |
|
< 0.001 |
|
< 0.001 |
|
> 5.0 |
98 |
1.737 (1.296-2.329) |
|
2.952 (1.987-4.386) |
|
Edmondson grade |
I+II |
225 |
|
< 0.001 |
|
0.001 |
|
III |
63 |
1.856 (1.340-2.570) |
|
2.047 (1.338-3.133) |
|
Microvascular invasion |
(-) |
129 |
|
< 0.001 |
|
< 0.001 |
|
(+) |
159 |
2.134 (1.587-2.869) |
|
3.056 (1.952-4.786) |
|
Major portal vein invasion |
(-) |
275 |
|
< 0.001 |
|
< 0.001 |
|
(+) |
13 |
3.905 (2.165-7.043) |
|
5.530 (2.855-10.711) |
|
Intrahepatic metastasis |
(-) |
220 |
|
< 0.001 |
|
< 0.001 |
|
(+) |
68 |
4.624 (3.360-6.364) |
|
5.580 (3.729-8.350) |
|
Multicentric occurrence |
(-) |
269 |
|
0.328 |
|
0.319 |
|
(+) |
19 |
1.340 (0.746-2.409) |
|
0.601 (0.221-1.635) |
|
AJCC T stage |
1 |
121 |
|
< 0.001 |
|
< 0.001 |
|
2+3+4 |
167 |
2.173 (1.610-2.934) |
|
3.090 (1.949-4.898) |
|
BCLC stage |
0+A |
164 |
|
< 0.001 |
|
< 0.001 |
|
B+C |
124 |
2.141 (1.606-2.853) |
|
3.732 (2.460-5.661) |
|
Albumin level (g/dL) |
> 3.5 |
258 |
|
0.008 |
|
0.001 |
|
≤ 3.5 |
30 |
1.813 (1.170-2.809) |
|
2.430 (1.418-4.163) |
|
AFP level (ng/mL) |
≤ 200 |
173 |
|
0.002 |
|
0.033 |
|
> 200 |
104 |
1.604 (1.197-2.150) |
|
1.552 (1.036-2.324) |
|
Etiology |
Non-viral |
40 |
|
0.025 |
|
0.154 |
|
viral |
248 |
1.390 (1.043-1.852) |
|
1.609 (0.836-3.094) |
|
Liver cirrhosis |
(-) |
144 |
|
0.004 |
|
0.554 |
|
(+) |
144 |
2.094 (1.271-3.449) |
|
1.126 (0.759-1.671) |
|
BCL9 expression |
(-) |
214 |
|
0.012 |
|
0.032 |
|
(+) |
74 |
1.508 (1.096-2.075) |
|
1.589 (1.042-2.423) |
|
Table 3.Multivariate analyses of disease-free survival and disease-specific survival in 288 hepatocellular carcinomas
Variable |
|
n |
Disease-free survival
|
Disease-specific survival
|
|
|
HR (95% CI) |
p-value |
HR (95% CI) |
p-value |
Edmondson grade |
I+II |
225 |
|
0.146 |
|
0.213 |
|
III |
63 |
1.298 (0.913-1.843) |
|
1.335 (0.847-2.104) |
|
BCLC stage |
0+A |
164 |
|
< 0.001 |
|
< 0.001 |
|
B+C |
124 |
2.279 (1.678-3.096) |
|
4.034 (2.594-6.273) |
|
Etiology |
Non-viral |
40 |
|
0.022 |
|
0.241 |
|
Viral |
248 |
1.833 (1.092-3.077) |
|
1.509 (0.759-3.001) |
|
Liver cirrhosis |
(-) |
144 |
|
0.011 |
|
0.068 |
|
(+) |
144 |
1.488 (1.095-2.023) |
|
1.488 (0.971-2.282) |
|
BCL9 expression |
(-) |
214 |
|
0.078 |
|
0.115 |
|
(+) |
74 |
1.351 (0.967-1.888) |
|
1.428 (0.917-2.225) |
|