Hypoxia upregulates hepatic angiopoietin-2 transcription to promote the progression of hepatocellular carcinoma

Table 1 Serum angiopoietin-2 and hypoxia-inducible factor-1α levels in patients with chronic liver diseases

Group	n	Ang-2		HIF-1α
		mean ± SD (μg/L)	> 35 μg/L, n (%)	mean ± SD (μg/L)	> 100 μg/L, n (%)
HCC	80	42.9 ± 5.1	162 (90.0)	145.6 ± 32.6	163 (90.6)
LC	50	26.2 ± 6.1a	3 (6.0)a	79.5 ± 28.4b	14 (28.0)b
CH	50	21.8 ± 6.9b	2 (4.0)b	60.1 ± 18.8b	1 (2.0)b
NC	50	16.9 ± 2.8b	0 (0.0)b	23.9 ± 4.2b	0 (0.0)b

^aP < 0.05, compared with the hepatocellular carcinoma group.

^bP < 0.01, compared with the hepatocellular carcinoma group.

Ang-2: Angiopoietin-2; HIF-lα: Hypoxia-inducible factor-1α; NC: Normal control; HCC: Hepatocellular carcinoma; LC: Liver cirrhosis; CH: Chronic hepatitis.

Table 2 Clinicopathological features associated with serum angiopoietin-2 levels in patients with hepatocellular carcinoma

Parameter	n	Ang-2 (mean ± SD, μg/L)	t value	P value
AFP (μg/L)			4.386	< 0.001
< 50	29	40.1 ± 8.1
≥ 50	51	45.2 ± 7.3
Portal vein invasion			10.11	< 0.001
With	49	48.2 ± 6.3
Without	31	39.4 ± 4.4
HBsAg			4.933	< 0.001
Negative	15	38.9 ± 6.1
Positive	65	45.8 ± 7.6
Tumor size			8.979	< 0.001
< 5 cm	38	40.3 ± 4.9
≥ 5 cm	42	48.7 ± 7.3
Liver cirrhosis			8.121	< 0.001
With	56	49.3 ± 6.1
Without	24	40.2 ± 8.4
Differentiation degree			9.408	< 0.001
Well/moderate	57	40.9 ± 4.1
Poor	23	48.7 ± 6.9
Gross classification			4.700	< 0.001
Unifocal	27	41.8 ± 6.3
Multifocal	53	47.7 ± 8.7
TNM			7.838	< 0.001
I-II	24	39.4 ± 4.9
III-IV	56	49.1 ± 8.5

AFP: Alpha-fetoprotein; Ang-2: Angiopoietin-2; HBsAg: Hepatitis B surface antigen; TNM: Tumor node metastasis.

Table 3 Dynamic alterations in angiopoietin-2 and hypoxia-inducible factor-1α during hepatocarcinogenesis in rats

Group	n	Ang-2		HIF-1α
		Liver (ng/mg)1	Serum (μg/L)	Liver (ng/mg)1	Serum (μg/L)
NC	12	69.7 ± 6.0	105.2 ± 19.2	9.7 ± 2.8	206.3 ± 9.6
HD	18	73.2 ± 17.0	140.2 ± 25.2	12.6 ± 3.2	270.2 ± 48.0
LC/PC	9	93.7 ± 11.2a	203.8 ± 23.8a	16.9 ± 2.6b	401.6 ± 89.4b
rHCC	9	107.6 ± 9. 8b	222.4 ± 23.3b	23.5 ± 8.9b	445.9 ± 69.5b

¹ng/per mg liver tissue.

^aP < 0.05, compared with the normal control group.

^bP < 0.01, compared with the normal control group.

Ang-2: Angiopoietin-2; HIF-lα: Hypoxia-inducible factor-1α; NC: Normal control; rHCC: Rat hepatocellular carcinoma; HD: Hepatocyte degeneration; LC: Liver cirrhosis; PC: Precancerosis.