Background
Methods
Patients and tissue sample specimens
Cell lines and cell culture
Cell transfection and stable cell lines construction
Tissue microarray and immunohistochemistry
Western blot analysis
Cell proliferation assay, clone formation assays, cell migration and invasion assays
Xenograft model with human HCC cells
Statistical analysis
Results
HRNR expression is related with poor prognosis of HCC
Category | Subcategory | Cases | HRNR expression | P value | |
---|---|---|---|---|---|
Low (n = 114) | High (n = 157) | ||||
Gender | male | 240 | 98 | 142 | |
female | 31 | 16 | 15 | 0.826 | |
Age (years) | ≤ 50 | 131 | 56 | 75 | |
> 50 | 140 | 58 | 82 | 0.253 | |
HCC family history | Yes | 18 | 8 | 10 | |
No | 253 | 106 | 147 | 0.665 | |
HBsAg | negative | 32 | 14 | 18 | |
positive | 239 | 100 | 139 | 0.837 | |
Child-pugh stage | A | 269 | 113 | 156 | |
B | 2 | 1 | 1 | 0.820 | |
AFP(ng/ml) | < 20 | 67 | 22 | 45 | |
≥20 | 204 | 92 | 112 | 0.078 | |
Edmonson Grading | I-II | 212 | 96 | 116 | |
III-IV | 59 | 18 | 41 | 0.042 | |
Tumor Size (cm) | ≤ 5 | 96 | 47 | 49 | |
> 5 | 175 | 67 | 108 | 0.089 | |
Liver Cirrhosis | absent | 55 | 27 | 28 | |
present | 216 | 87 | 129 | 0.237 | |
Capsulation | capsulated | 171 | 76 | 95 | |
non-caspulated | 100 | 38 | 62 | 0.300 | |
Tumor Number | single | 185 | 85 | 100 | |
multiple | 86 | 29 | 57 | 0.058 | |
Vascular Invasion | Yes | 56 | 16 | 40 | |
No | 215 | 98 | 117 | 0.022 | |
TNM Stage | I-II | 152 | 80 | 72 | |
III-IV | 119 | 34 | 85 | < 0.001 |
Variables |
n
| DFS | OS |
P
| |||||
---|---|---|---|---|---|---|---|---|---|
1-yr | 3-yr | 5-yr |
P
| 1-yr | 3-yr | 5-yrs | |||
Gender | |||||||||
Male | 240 | 41.7% | 29.2% | 25.3% | 66.7% | 43.8% | 37.1% | ||
Female | 31 | 54.8% | 38.7% | 38.7% | 0.095 | 83.9% | 61.3% | 54.8% | 0.034 |
Age (years) | |||||||||
≤ 50 | 131 | 41.2% | 31.3% | 28.2% | 67.2% | 45.0% | 37.4% | ||
> 50 | 140 | 48.6% | 29.3% | 25.4% | 0.565 | 70.0% | 46.4% | 40.7% | 0.619 |
HCC family history | |||||||||
Yes | 18 | 50.0% | 27.8% | 22.2% | 83.3% | 55.6% | 55.6% | ||
No | 253 | 42.7% | 30.4% | 27.1% | 0.864 | 67.6% | 45.1% | 37.9% | 0.148 |
HBsAg | |||||||||
Negative | 32 | 59.4% | 37.5% | 37.5% | 78.1% | 50.0% | 43.8% | ||
Positive | 239 | 41.0% | 29.3% | 25.3% | 0.148 | 67.4% | 45.2% | 38.5% | 0.366 |
Child-pugh stage | |||||||||
A | 269 | 43.1% | 30.1% | 26.6% | 68.8% | 45.7% | 39.0% | ||
B | 2 | 50.0% | 50.0% | 50.0% | 0.485 | 50.0% | 50.0% | 50.0% | 0.799 |
AFP (ng/ml) | |||||||||
≤ 20 | 67 | 55.2% | 35.8% | 34.3% | 73.1% | 52.2% | 47.8% | ||
> 20 | 204 | 39.2% | 28.4% | 24.3% | 0.078 | 67.2% | 43.6% | 36.2% | 0.063 |
Edmondson grading | |||||||||
I-II | 212 | 47.6% | 34.4% | 30.5% | 71.7% | 49.5% | 43.8% | ||
III-IV | 59 | 27.1% | 15.3% | 13.6% | < 0.001 | 57.6% | 32.2% | 22.0% | 0.002 |
Tumor size (cm) | |||||||||
≤ 5 | 96 | 66.7% | 50.0% | 42.4% | 87.5% | 67.7% | 60.4% | ||
> 5 | 175 | 29.7% | 19.4% | 18.3% | < 0.001 | 58.3% | 33.7% | 27.4% | < 0.001 |
Liver Cirrhosis | |||||||||
Absent | 55 | 41.8% | 30.9% | 27.3% | 76.4% | 47.3% | 41.8% | ||
Present | 216 | 43.5% | 30.1% | 26.7% | 0.973 | 66.7% | 45.4% | 38.4% | 0.399 |
Capsulation | |||||||||
Capsulated | 171 | 53.8% | 37.4% | 35.6% | 78.4% | 55.0% | 49.1% | ||
Non-caspulated | 100 | 25.0% | 18.0% | 11.6% | < 0.001 | 52.0% | 30.0% | 22.0% | < 0.001 |
Tumor number | |||||||||
Single | 185 | 51.9% | 38.4% | 34.0% | 75.7% | 55.1% | 49.7% | ||
Multiple | 86 | 24.4% | 12.7% | 11.1% | < 0.001 | 53.5% | 25.6% | 16.3% | < 0.001 |
Vascular invasion | |||||||||
Yes | 56 | 12.5% | 7.1% | 5.4% | 32.1% | 16.1% | 8.9% | ||
No | 215 | 51.2% | 36.3% | 32.4% | < 0.001 | 78.1% | 53.5% | 47.0% | < 0.001 |
HRNR expression | |||||||||
Low | 114 | 61.4% | 49.1% | 45.3% | 78.9% | 65.8% | 63.1% | ||
High | 157 | 29.9% | 16.6% | 13.4% | < 0.001 | 61.1% | 31.2% | 21.6% | < 0.001 |
TNM stage | |||||||||
I-II | 152 | 59.9% | 44.7% | 40.6% | 84.9% | 63.2% | 57.9% | ||
III-IV | 119 | 21.8% | 11.8% | 9.2% | < 0.001 | 47.9% | 23.5% | 15.1% | < 0.001 |
Variables | DFS | OS | ||||
---|---|---|---|---|---|---|
HR | 95%CI |
P
| HR | 95%CI |
P
| |
Tumor size (cm) (> 5 vs ≤ 5) | 1.849 | 1.343–2.546 | < 0.001 | 1.829 | 1.276–2.621 | 0.001 |
Capsulation (capsulated vs non-caspulated) | 0.621 | 0.458–0.842 | 0.002 | 0.644 | 0.461–0.899 | 0.010 |
Tumor number (single vs mulitiple) | 0.614 | 0.456–0.828 | 0.001 | 0.607 | 0.440–0.838 | 0.002 |
Vascular invasion (Yes vs No) | 1.817 | 1.274–2.590 | 0.001 | 1.691 | 1.156–2.474 | 0.007 |
HRNR expression (High vs Low) | 2.209 | 1.627–2.998 | < 0.001 | 2.459 | 1.736–3.484 | < 0.001 |