α-fetoprotein, vascular endothelial growth factor receptor-1 and early recurrence of hepatoma

Table 1 Characteristics of hepatocellular carcinoma patients according to their bone marrow-α-fetoprotein and peripheral blood-α-fetoprotein mRNA profile

		BM-AFP mRNA		P value	PH-AFP mRNA		P value
		Positive (n = 34)	Negative (n = 80)		Positive (n = 6)	Negative (n = 105)
Sex	Male	27	67	0.5774	5	86	0.9294
	Female	7	13		1	19
Age (yr)	≤ 60	19	34	0.1900	5	47	0.0655
	> 60	15	46		1	58
HBsAg	+	19	30	0.0697	3	45	0.7312
	-	15	50		3	60
HCV	+	12	34	0.4731	2	43	0.7116
	-	22	46		4	62
Albumin	≤ 4.0 mg/dL	13	33	0.7641	3	41	0.5937
	> 4.0 mg/dL	21	47		3	64
Total bilirubin	≤ 0.7 mg/dL	21	45	0.5853	4	60	0.6461
	≥ 0.8 mg/dL	13	35		2	45
ICGR15	≤ 15%	22	39	0.1181	3	56	0.8736
	> 15%	12	41		3	49
Anatomical resection	Yes	25	54	0.5231	4	73	0.8826
	No	9	26		2	32
AFP	≤ 200 ng/mL	21	57	0.3189	1	76	0.0040
	> 200 ng/nL	13	23		5	29
AFPL3	≤ 15%	21	58	0.2556	2	76	0.0418
	> 15%	13	22		4	29
PIVKA-II	≤ 40 mAU/mL	8	30	0.1477	1	36	0.3732
	> 40 mAU/mL	26	50		5	69
Tumor number	Solitary	25	57	0.8804	2	78	0.0259
	Multiple	9	22		4	26
Tumor size	≤ 2 cm	2	10	0.2922	0	12	0.3806
	> 2 cm	32	70		6	93
Differentiation	Well	0	7	0.0737	0	7	0.5859
	Moderately	26	49		3	70
	Poorly	7	24		3	27
vp	Positive	14	18	0.0423	5	25	0.0014
	Negative	20	62		1	80
vv	Positive	3	4	0.4366	1	5	0.2098
	Negative	31	76		5	100
im	Positive	12	18	0.1558	4	25	0.0201
	Negative	22	62		2	80
Noncancerous liver		11	28	0.6833	1	36	0.3501
Liver cirrhosis
Non liver cirrhosis		23	49		5	66

BM: Bone marrow; PH: Peripheral blood; AFP: α-fetoprotein; HBsAg: Hepatitis B surface antigen; HCV: Anti-hepatitis C virus antibody; AR: Patients who underwent anatomical resection; ICGR15: Indocyanine green retention rate at 15 min; vp: Microscopic tumor thrombus in the portal vein; vv: Microscopic tumor thrombus in the hepatic vein; im: Microscopic intrahepatic metastasis.

Table 2 Characteristics of hepatocellular carcinoma patients according to their bone marrow-vascular endothelial growth factor receptor-1 and peripheral blood-vascular endothelial growth factor receptor-1 mRNA profile

		BM-VEGFR1		P value	PH-VEGFR1		P value
		High (n = 81)	Low (n = 33)		High (n = 78)	Low (n = 26)
Sex	Male	67	27	0.9090	64	22	0.7647
	Female	14	6		14	4
Age (yr)	≤ 60	40	13	0.3322	37	12	0.9097
	> 60	41	20		41	14
HBsAg	+	35	14	0.9387	34	12	0.8197
	-	46	19		44	14
HCV	+	36	10	0.1628	32	9	0.5624
	-	45	23		46	17
Albumin	≤ 4.0 mg/dL	38	8	0.0252	27	12	0.2926
	> 4.0 mg/dL	43	25		51	14
Total bilirubin	≤ 0.7 mg/dL	48	18	0.6439	51	11	0.0378
	≥ 0.8 mg/dL	33	15		27	15
ICGR15	≤ 15%	41	20	0.3322	44	13	0.5695
	> 15%	40	13		34	13
Anatomical resection	Yes	55	24	0.6124	56	18	0.8026
	No	26	9		22	8
AFP	≤ 200 ng/mL	54	24	0.5278	57	16	0.2653
	> 200 ng/nL	27	9		21	10
AFPL3	≤ 15%	54	25	0.3399	59	15	0.0802
	> 15%	27	8		19	11
PIVKA-II	≤ 40 mAU/mL	24	14	0.1888	25	10	0.5491
	> 40 mAU/mL	57	19		53	16
Tumor number	Solitary	53	29	0.0068	55	18	0.8867
	Multiple	28	3		23	7
Tumor size	≤ 2 cm	9	3	0.7499	10	2	0.4784
	> 2 cm	72	30		68	24
Differentiation	Well	4	3	0.1151	6	1	0.1614
	Moderately	51	25		56	11
	Poorly	26	5		16	14
vp	Positive	26	6	0.1337	21	7	...
	Negative	55	27		57	19
vv	Positive	6	1	0.3773	4	1	0.7913
	Negative	75	32		74	25
im	Positive	23	7	0.4296	24	5	0.2559
	Negative	58	26		54	21
Noncancerous liver cirrhosis		34	5	0.0061	26	9	0.9962
Non liver cirrhosis		45	27		49	17

BM: Bone marrow; PH: Peripheral blood; AFP: α-fetoprotein; HBsAg: Hepatitis B surface antigen; VEGFR: Vascular endothelial growth factor receptor; HCV: Anti-hepatitis C virus antibody; AR: Patients who underwent anatomical resection; ICGR15: Indocyanine green retention rate at 15 min; vp: Microscopic tumor thrombus in the portal vein; vv: Microscopic tumor thrombus in the hepatic vein; im: Microscopic intrahepatic metastasis.

Table 3 Clinical factors related to early hepatocellular carcinoma recurrence after curative hepatectomy

		Recurrence over 1 year (77)	Recurrence within 1 year (37)	P value
Sex	Male	64	30	0.7980
	Female	13	7
Age (yr)	≤ 60	30	23	0.0200
	> 60	47	14
HBsAg	+	24	25	0.0002
	-	53	12
HCV	+	34	12	0.2322
	-	43	25
Albumin	≤ 4.0 mg/dL	24	22	0.0039
	> 4.0 mg/dL	53	15
Total bilirubin	≤ 0.7 mg/dL	47	19	0.3266
	≥ 0.8 mg/dL	30	18
ICGR15	≤ 15%	43	18	0.4708
	> 15%	34	19
Anatomical resection	Yes	55	24	0.4769
	No	22	13
AFP	≤ 200 ng/mL	59	19	0.0066
	> 200 ng/nL	18	18
AFPL3	≤ 15%	58	21	0.0442
	> 15%	19	16
PIVKA-II	≤ 40 mAU/mL	32	6	0.0072
	> 40 mAU/mL	45	31
Tumor number	Solitary	62	20	0.0021
	Multiple	14	17
Tumor size	≤ 2 cm	36	6	0.0016
	> 2 cm	41	31
Differentiation	Well	7	0	0.1631
	Moderately	52	13
	Poorly	18	24
vp	Positive	11	16	< 0.0001
	Negative	66	21
vv	Positive	2	5	0.0230
	Negative	75	32
im	Positive	13	17	0.0010
	Negative	64	20
BM VEGFR1	Low	24	9	0.4506
	High	53	28
PH VEGFR1	Low	18	8
	High	54	24
BM AFP mRNA	Positive	17	17	0.0091
	Negative	60	20
PH AFP mRNA	Positive	2	4	0.0569
	Negative	74	31
BM-AFP mRNA/BM-VEGFR1	Negative/low	20	3	0.0228
	Negative/high	40	17
	Positive/low	4	6
	Positive/high	13	11

BM: Bone marrow; PH: Peripheral blood; AFP: α-fetoprotein; HBsAg: Hepatitis B surface antigen; VEGFR: Vascular endothelial growth factor receptor; HCV: Anti-hepatitis C virus antibody; ICGR15: Indocyanine green retention rate at 15 min; vp: Microscopic tumor thrombus in the portal vein; vv: Microscopic tumor thrombus in the hepatic vein; im: Microscopic intrahepatic metastasis.

Table 4 Multivariate analyses of variables that are predictive of early hepatocellular carcinoma recurrence after curative hepatectomy

	P value	Risk ratio	95% CI
Age ≤ 60 yr	0.0899	3.147	0.836-11.838
HBsAg +	0.3601	1.821	0.504-6.571
Albumin ≤ 4.0 mg/dL	0.0038	6.536	1.832-23.256
AFP > 200 ng/nL	0.2571	2.330	0.539-10.067
AFPL3 ≤ 15%	0.4379	1.869	0.385-9.090
PIVKA-II > 40 mAU/mL	0.1494	2.959	0.677-12.987
Tumor number solitary	0.9127	1.088	0.240-4.938
Tumor size > 3 cm	0.1177	3.026	0.756-12.114
vp positive	0.0069	6.639	1.681-26.219
vv positive	0.2221	0.234	0.023-2.408
im positive	0.2307	2.508	0.557-11.289
BM AFP mRNA: positive	0.0761	2.704	0.901-8.113

CI: Confidence interval; BM: Bone marrow; AFP: α-fetoprotein; HBsAg: Hepatitis B surface antigen; vp: Microscopic tumor thrombus in the portal vein; vv: Microscopic tumor thrombus in the hepatic vein; im: Microscopic intrahepatic metastasis.