Background
Methods
Study population
Immunohistochemical analysis
Evaluation of Immunohistochemical staining
Real -time quantitative polymerase chain reaction (qRT-PCR)
Statistical analysis
Results
The expression of c-Myc protein and mRNA in HCC and adjacent tissues
Group | N | Expression of C-MYC | |
---|---|---|---|
High (++~+++) | Low (−~+) | ||
Normal liver tissues | 20 | 0(0.0%) | 20(100.0%) |
Adjacent tissuesa | 84 | 55(65.5%) | 29 (34.5%) |
HCC tissuesa | 84 | 50(59.5%) | 34(40.5%) |
Correlation between 15 clinicopathological characteristics and c-Myc protein expression in HCC and adjacent tissues
Variables | Cases | c-Myc expression in HCC tissues | P value | c-Myc expression in adjacent tissues | P value | ||
---|---|---|---|---|---|---|---|
Low | High | Low | High | ||||
Age(yrs) | |||||||
> =60 | 16 | 4(25.0%) | 12(75.0%) | 0.161 | 3(18.8%) | 13(81.2%) | 0.140 |
< 60 | 68 | 30(44.1%) | 38(55.9%) | 26(38.2%) | 42(61.8%) | ||
Sex | |||||||
Male | 68 | 29(42.6%) | 39(57.4%) | 0.403 | 21(30.9%) | 47(69.1%) | 0.148 |
Female | 16 | 5(31.3%) | 11(68.7%) | 8(50.0%) | 8(50.0%) | ||
HbsAg | |||||||
Positive | 72 | 30(41.7%) | 42(58.3%) | 0.586 | 25(34.7%) | 47(65.3%) | 0.925 |
Negative | 12 | 4(33.3%) | 8(66.7%) | 4(33.3%) | 8(66.7%) | ||
ALT(U/L) | |||||||
≥ 80 | 9 | 3(33.3%) | 6(66.7%) | 0.644 | 5(55.6%) | 4(44.4%) | 0.160 |
<80 | 75 | 31(41.3%) | 44(58.7%) | 24(32.0%) | 51(68.0%) | ||
PLT(×109) | |||||||
> 100 | 74 | 33(44.6%) | 41(55.4%) | 0.036 | 24(32.4%) | 50(67.6%) | 0.273 |
≤ 100 | 10 | 1(10.0%) | 9(90.0%) | 5(50.0%) | 5(50.0%) | ||
Cirrhosis | |||||||
Yes | 64 | 22(34.4%) | 42(65.6%) | 0.042 | 19(29.7%) | 45(70.3%) | 0.095 |
No | 20 | 12(60.0%) | 8(40.0%) | 10(50.0%) | 10(50.0%) | ||
AFP(ug/L) | |||||||
≥ 20 | 48 | 22(45.8%) | 26(51.2%) | 0.248 | 19(39.6%) | 29(60.4%) | 0.260 |
<20 | 36 | 12(33.3%) | 24(66.7%) | 10(27.8%) | 26(72.2%) | ||
Tumor size (cm) | |||||||
≥ 5 | 50 | 25(50.0%) | 25(50.0%) | 0.031 | 19(38.0%) | 31(62.0%) | 0.416 |
<5 | 34 | 9(26.5%) | 25(73.5%) | 10(29.4%) | 24(70.6%) | ||
Tumor number | |||||||
Single | 62 | 21(33.9%) | 41(66.1%) | 0.038 | 20(32.3%) | 42(67.7%) | 0.463 |
Multiple | 22 | 13(59.1%) | 9(40.9%) | 9(40.9%) | 13(59.1%) | ||
Differentiation | |||||||
I-II | 62 | 24(38.7%) | 38(61.3%) | 0.580 | 25(40.3%) | 37(59.7%) | 0.061 |
III | 22 | 10(45.5%) | 12(54.5%) | 4(18.2%) | 18(81.8%) | ||
TNM stage | |||||||
I | 55 | 20(36.4%) | 35(63.6%) | 0.290 | 18(32.7%) | 37(67.3%) | 0.633 |
II-III | 29 | 14(48.3%) | 15(51.7%) | 11(37.9%) | 18(62.1%) | ||
PVTT | |||||||
Yes | 11 | 8(72.7%) | 3(27.3%) | 0.019 | 4(36.4%) | 7(63.6%) | 0.890 |
No | 73 | 26(35.6%) | 47(64.4%) | 25(34.2%) | 48(65.8%) | ||
Tumor Encapsulation | |||||||
Complete | 64 | 23(35.9%) | 41(64.1%) | 0.130 | 17(26.6%) | 47(73.4%) | 0.006 |
None | 20 | 11(55.0%) | 9(45.0%) | 12(60.0%) | 8(40.0%) | ||
Recurrence | |||||||
Yes | 58 | 30(51.7%) | 28(48.3%) | 0.002 | 21(36.2%) | 37(63.8%) | 0.628 |
No | 26 | 4(15.4%) | 22(84.6%) | 8(30.8%) | 18(69.2%) | ||
Complication | |||||||
No | 73 | 27(37.0%) | 46(63.0%) | 0.177 | 27(37.0%) | 46(63.0%) | 0.221 |
Yes | 11 | 7(63.6%) | 4(36.4%) | 2(18.2%) | 9(81.8%) |
Independent prognostic factors of HCC
Variables |
n
| DFS |
P
| OS | P | ||||
---|---|---|---|---|---|---|---|---|---|
1-yr | 3-yrs | 5-yrs | 1-yr | 3-yrs | 5-yrs | ||||
Sex | |||||||||
Male | 68 | 47.1% | 36.8% | 30.5% | 0.433 | 79.4% | 50.0% | 41.2% | 0.478 |
Female | 16 | 56.3% | 37.5% | 37.5% | 87.5% | 56.3% | 50.0% | ||
Age(yrs) | |||||||||
< 60 | 68 | 45.6% | 32.4% | 27.7% | 0.104 | 82.4% | 48.5% | 39.7% | 0.391 |
≥ 60 | 16 | 62.5% | 56.3% | 49.2% | 75.0% | 62.5% | 56.3% | ||
PLT(×109) | |||||||||
<100 | 10 | 80.0% | 60.0% | 60.0% | 0.053 | 100% | 80.0% | 70.0% | 0.076 |
≥ 100 | 74 | 44.6% | 33.8% | 28.0% | 78.4% | 47.3% | 39.2% | ||
HbsAg | |||||||||
Positive | 72 | 47.2% | 38.9% | 33.0% | 0.700 | 79.2% | 50.0% | 44.4% | 0.882 |
Negative | 12 | 58.3% | 25.0% | 25.0% | 91.7% | 58.3% | 33.3% | ||
AFP(μg/L) | |||||||||
<20 | 36 | 52.8% | 38.9% | 38.9% | 0.336 | 83.3% | 50.0% | 44.4% | 0.750 |
≥ 20 | 48 | 45.8% | 35.4% | 26.3% | 79.2% | 52.1% | 41.7% | ||
Ascites | |||||||||
No | 68 | 52.9% | 39.7% | 35.0% | 0.093 | 83.8% | 51.5% | 44.1% | 0.551 |
Yes | 16 | 31.3% | 25.0% | 18.8% | 68.8% | 50.0% | 37.5% | ||
Cirrhosis | |||||||||
No | 24 | 45.0% | 35.0% | 30.0% | 0.685 | 95.0% | 60.0% | 45.0% | 0.485 |
Yes | 60 | 50.0% | 37.5% | 32.4% | 76.6% | 48.4% | 42.2% | ||
Tumor number | |||||||||
Single | 62 | 59.7% | 43.5% | 36.7% | 0.002 | 85.5% | 61.3% | 51.6% | < 0.001 |
Multiple | 22 | 18.2% | 18.2% | 18.2% | 68.2% | 22.7% | 18.2% | ||
PVTT | |||||||||
No | 73 | 54.8% | 41.1% | 35.3% | < 0.001 | 87.7% | 56.2% | 47.9% | < 0.001 |
Yes | 11 | 9.1% | 9.1% | 9.1% | 36.4% | 18.2% | 9.1% | ||
Tumor size (cm) | |||||||||
< 5 | 34 | 64.7% | 47.1% | 41.2% | 0.055 | 97.1% | 67.6% | 52.9% | 0.040 |
≥ 5 | 50 | 38.0% | 30.0% | 25.7% | 70.0% | 40.0% | 36.0% | ||
Tumor Encapsulation | |||||||||
None | 20 | 30.0% | 25.0% | 15.0% | 0.013 | 60.0% | 45.0% | 30.0% | 0.081 |
Complete | 64 | 54.7% | 40.6% | 37.3% | 87.5% | 53.1% | 46.9% | ||
Resection margin | |||||||||
<2 cm | 45 | 40.0% | 26.7% | 24.4% | 0.106 | 80.0% | 40.0% | 28.9% | 0.007 |
≥ 2 cm | 39 | 59.0% | 48.7% | 40.5% | 82.1% | 64.1% | 59.0% | ||
Complication | |||||||||
No | 73 | 49.3% | 38.4% | 32.8% | 0.407 | 84.9% | 53.4% | 45.2% | 0.095 |
Yes | 11 | 45.5% | 27.3% | 27.3% | 54.5% | 36.4% | 27.3% | ||
Tumor differetiation | |||||||||
I-II | 62 | 54.8% | 41.9% | 35.0% | 0.212 | 85.5% | 56.5% | 48.4% | 0.037 |
III-IV | 22 | 31.8% | 22.7% | 22.7% | 68.2% | 36.4% | 27.3% | ||
Blood inflow occlusion | |||||||||
Yes | 31 | 41.9% | 29.0% | 20.7% | 0.182 | 77.4% | 48.4% | 35.5% | 0.300 |
No | 53 | 52.8% | 41.5% | 37.7% | 83.0% | 52.8% | 47.2% | ||
Blood transfusion | |||||||||
Yes | 25 | 20.0% | 4.0% | 4.0% | < 0.001 | 56.0% | 12.0% | 4.0% | < 0.001 |
No | 59 | 61.0% | 50.8% | 43.7% | 91.5% | 67.8% | 59.3% | ||
Blood loss (mL) | |||||||||
≤ 1000 | 73 | 54.8% | 42.5% | 36.7% | < 0.001 | 86.3% | 58.9% | 49.3% | < 0.001 |
> 1000 | 11 | 9.1% | 0.0% | 0.0% | 45.5% | 0.0% | 0.0% | ||
Operative time(min) | |||||||||
≤ 180 | 42 | 66.7% | 54.8% | 47.3% | < 0.001 | 92.9% | 73.8% | 64.3% | < 0.001 |
> 180 | 42 | 31.0% | 19.0% | 16.7% | 69.0% | 28.6% | 21.4% | ||
TNM stage | |||||||||
I | 55 | 60.0% | 43.6% | 39.7% | 0.002 | 90.9% | 60.0% | 52.7% | 0.001 |
II-III | 29 | 27.6% | 24.1% | 17.2% | 62.1% | 34.5% | 24.1% | ||
c-Myc | |||||||||
Low | 34 | 17.6% | 11.8% | 11.8% | < 0.001 | 64.7% | 20.6% | 14.7% | < 0.001 |
High | 50 | 70.0% | 54.0% | 45.9% | 92.0% | 72.0% | 62.0% |
Variables
|
DFS
|
OS
| ||||
---|---|---|---|---|---|---|
HR | 95%CI |
P
| HR | 95%CI |
P
| |
Blood transfusion | 1.922 | 1.017–3.635 | 0.044 | 2.856 | 1.465–5.567 | 0.002 |
TNM stage | 2.143 | 1.220–3.766 | 0.008 | 2.191 | 1.169–4.108 | 0.014 |
c-Myc | 0.364 | 0.194–0.686 | 0.002 | 0.284 | 0.148–0.548 | < 0.001 |
Low expression of c-Myc predicts short-term recurrence and the poor outcomes in patients with HCC.
Recurrence | N | c-Myc expression | |
---|---|---|---|
High | Low | ||
0–1(yrs) a,b | 43 | 16(37.2%) | 27 (62.8%) |
> 1(yrs)c | 14 | 12(85.7%) | 2 (14.3%) |
No recurrence | 27 | 23(85.2%) | 4(14.8%) |
Combining c-Myc expression with TGF-β1 or/and ELF reveals improved prognostic accuracy for HCC
c-Myc
|
TGF-β1
|
r
|
P value
| ||
---|---|---|---|---|---|
+++ | ++ | -~+ | |||
+++ | 7 | 5 | 12 | −0.228 | 0.037 |
++ | 9 | 3 | 15 | ||
-~+ | 15 | 11 | 7 |
c-Myc
|
ELF
|
r
|
P value
| ||
---|---|---|---|---|---|
+++ | ++ | -~+ | |||
+++ | 12 | 1 | 11 | 0.217 | 0.048 |
++ | 4 | 11 | 12 | ||
-~+ | 7 | 5 | 21 |