Background
Methods
In vitro study
Cell culture
HSC conditioned (CM) medium preparation
Scratch assays
Polymerase chain reaction (PCR) analysis
Western blotting
Clinicopathological study
Patient selection
Immunohistochemical assessment of HIF-1α
Statistics
Results
Tumor malignancy is enhanced in the liver by HSCs
HIF-1α expression in liver metastasis determines patient prognosis
Factors | Low expression (n = 21) | High expression (n = 54) | p value | |
---|---|---|---|---|
Primary factors | ||||
Location | Colon/rectum | 12/9 | 34/20 | 0.6433 |
Depth | < SS/≥ SS | 2/19 | 5/49 | 0.9718 |
Diff. | Diff/undiff | 20/1 | 51/3 | 0.8896 |
Lymphatic invasion | −/+ | 9/12 | 20/33 | 0.6614 |
Vessel invasion | −/+ | 5/16 | 17/37 | 0.5068 |
LN metastasis | −/+ | 8/13 | 24/30 | 0.6165 |
Metastatic factors | ||||
Meta. period | Meta/syn | 10/11 | 22/32 | 0.5895 |
Tumor size (cm) | < 5/≥ 5 | 15/6 | 42/12 | 0.5678 |
Tumor number | < 5/≥ 5 | 17/4 | 43/11 | 0.8973 |
H class | H1/H2.3 | 12/9 | 34/20 | 0.6433 |
Grade | A/B.C | 12/9 | 26/28 | 0.4836 |
Adjuvant therapy | −/+ | 8/13 | 22/32 | 0.8337 |
Hepatectomy | Minor/major | 16/5 | 46/8 | 0.3555 |
CA19-9a | < 100/≥ 100 | 16/4 | 43/4 | 0.2014 |
CEAa | < 10/≥ 10 | 12/8 | 27/20 | 0.8461 |
Factors | Low expression (n = 24) | High expression (n = 51) | p value | |
---|---|---|---|---|
Primary factors | ||||
Location | Colon/rectum | 16/8 | 30/21 | 0.5130 |
Depth | < SS/≥ SS | 1/23 | 6/45 | 0.2601 |
Diff. | Diff/undiff | 23/1 | 48/3 | 0.7528 |
Lymphatic invasion | −/+ | 10/14 | 19/31 | 0.6476 |
Vessel invasion | −/+ | 6/18 | 16/35 | 0.5684 |
LN metastasis | −/+ | 9/15 | 23/28 | 0.5334 |
Metastatic factors | ||||
Meta. period | Meta/syn | 7/17 | 25/26 | 0.1005 |
Tumor size (cm) | < 5≥ 5 | 18/6 | 39/12 | 0.8896 |
Tumor number | < 5/≥ 5 | 19/5 | 41/10 | 0.9018 |
H class | H1/H2.3 | 14/10 | 32/19 | 0.7150 |
Grade | A/B.C | 11/13 | 27/24 | 0.5656 |
Adjuvant therapy | −/+ | 8/16 | 22/29 | 0.4188 |
Hepatectomy | Minor/major | 17/7 | 45/6 | 0.1633 |
CA19-9a | < 100/≥ 100 | 19/1 | 40/7 | 0.2196 |
CEAa | < 10/≥ 10 | 10/10 | 29/18 | 0.3758 |
Factors | 5-year survival (%) | Univariate | Multivariate | |||
---|---|---|---|---|---|---|
HR (95% CI) | p value | HR (95% CI) | p value | |||
Primary factors | ||||||
Location | Colon/rectum | 56.0/58.0 | 1.03 (0.46–2.24) | 0.9357 | ||
Depth | < SS/> SS | 65.6/58.9 | 0.93 (0.28–5.81) | 0.9242 | ||
Diff. | Diff/undiff | 59.1/0 | 23.90 (4.58–112.20) | < 0.0001 | 20.87 (3.78–107.13) | 0.0013 |
Lymphatic invasion | −/+ | 66.5/53.7 | 0.93 (0.43–2.13) | 0.9569 | ||
Vessel invasion | −/+ | 59.9/56.7 | 1.16 (0.53–2.75) | 0.7172 | ||
LN metastasis | −/+ | 70.3/48.7 | 1.53 (0.70–3.59) | 0.3019 | ||
HIF-1α | −/+ | 60.4/54.6 | 1.21 (0.55–2.85) | 0.6424 | ||
Metastatic factors | ||||||
Meta. period | Meta/syn | 69.0/49.8 | 1.79 (0.79–4.59) | 0.1826 | ||
Tumor size (cm) | < 5/> 5 | 60.5/47.2 | 1.85 (0.81–4.04) | 0.1213 | ||
Tumor number | < 5/> 5 | 58.4/51.1 | 1.67 (0.68–3.72) | 0.2231 | ||
H class | H1/H2.3 | 63.8/46.0 | 2.22 (1.02–4.96) | 0.0400 | 1.19 (0.41–4.31) | 0.7591 |
Grade | A/B.C | 72.7/44.2 | 2.89 (1.27–7.42) | 0.0119 | 2.37 (0.20-0.61) | 0.1996 |
Adjuvant therapy | −/+ | 68.3/54.4 | 1.22 (0.53–3.13) | 0.6514 | ||
Hepatectomy | Minor/major | 52.6/64.7 | 0.68 (0.20–1.79) | 0.4832 | ||
HIF-1α | −/+ | 75.8/54.9 | 3.26 (1.24–11.17) | 0.0220 | 2.85 (1.04–10.01) | 0.0422 |
CA19-9 | < 100/> 100 | 28.2/37.5 | 0.73 (0.27–2.53) | 0.2557 | ||
CEA | < 10/> 10 | 57.4/55.1 | 1.45 (0.60–3.84) | 0.4164 |
Factors | 3-year survival (%) | Univariate | Multivariate | |||
---|---|---|---|---|---|---|
HR (95% CI) | p value | HR (95% CI) | p value | |||
Primary factors | ||||||
Location | Colon/rectum | 27.3/30.7 | 1.17 (0.67–2.10) | 0.4980 | ||
Depth | < SS/> SS | 18.8/31.2 | 0.77 (0.23–1.91) | 0.6370 | ||
Diff. | Diff/undiff | 31.1/0 | 3.16 (1.00–8.92) | 0.0466 | 2.14 (0.50–6.27) | 0.2650 |
Lymphatic invasion | −/+ | 32.6/31.0 | 1.05 (0.58–1.87) | 0.7784 | ||
Vessel invasion | −/+ | 28.0/32.7 | 0.92 (0.50–1.64) | 0.9157 | ||
LN metastasis | −/+ | 50.7/18.4 | 1.91 (1.07–3.51) | 0.0146 | 2.03 (1.12–3.79) | 0.0186 |
HIF-1α | −/+ | 33.3/31.2 | 1.03 (0.56–1.83) | 0.9122 | ||
Metastatic factors | ||||||
Meta. period | Meta/syn | 39.6/23.8 | 1.71 (0.97–3.13) | 0.0693 | ||
Tumor size (cm) | < 5/> 5 | 26.1/41.7 | 0.95 (0.52–1.86) | 0.8708 | ||
Tumor number | < 5/> 5 | 30.8/27.8 | 1.58 (0.79–2.94) | 0.1647 | ||
H class | H1/H2.3 | 31.3/27.9 | 1.55 (0.88–2.70) | 0.1224 | ||
Grade | A/B.C | 37.6/22.7 | 2.02 (1.16–3.58) | 0.0119 | 2.21 (1.26–3.94) | 0.0057 |
Adjuvant therapy | −/+ | 30.2/23.8 | 1.54 (0.96–3.34) | 0.1681 | ||
Hepatectomy | Minor/major | 28.8/46.2 | 0.97 (0.44–1.92) | 0.9361 | ||
HIF-1α | −/+ | 52.2/19.6 | 2.48 (1.30–5.16) | 0.0073 | 2.40 (1.25–5.01) | 0.0079 |
CA19-9 | < 100/> 100 | 63.5/37.5 | 1.71 (0.74–4.98) | 0.5631 | ||
CEA | < 10/> 10 | 27.6/30.1 | 1.19 (0.66–2.20) | 0.5739 |