Folate receptor-positive circulating tumor cells might function as potential biomarkers for hepatocellular carcinoma

Table 1 Patient characteristics, mean ± SD/median (interquartile ranges)

Characteristics	Number of patients
HCC
Age, years	56.2 ± 12.3
Sex
Male	92
Female	15
Tumor size (mm)	6.26 ± 4.1
Tumor stage
BCLC-A	37
BCLC-B	41
BCLC-C	39
Vascular invasion
Macro invasion	20
Micro invasion	15
No invasion	72
Before treatment	84
After R0 resection	14
After conservative treatment	9
Benign disease
Age	54.3 (25-70)
Histological type
Liver cirrhosis	7
Hemangioma	10
Hepatolithiasis	4

HCC: Hepatocellular carcinoma; BCLC: Barcelona Clinic Liver Cancer.

Table 2 Relationships of circulating tumor cell levels between different patients` characteristic, mean ± SD

Characteristic	Number of patients	CTC units	P value
Sex			0.92
Female	12	14.4 ± 5.8
male	72	14.6 ± 4.9
Age			0.62
≤ 50	31	14.2 ± 3.8
> 50	53	14.8 ± 5.5
Tumor diameter			0.048a
< 5 cm	45	12.7 ± 4.9
> 5 cm	39	15.8 ± 5.0
Tumor stage			< 0.001c
BCLC (A + B)	63	12.7 ± 3.2
BCLC (C)	21	20.4 ± 5.3
Vascular invasion			0.201
No invasion	58	14.1 ± 5.01
Micro-vascular invasion	12	12.2 ± 2.09
Macro-vascular invasion	14	18.8 ± 4.29	0.0023b
Satellite			0.21
No	76	14.6 ± 5.1
yes	8	12.5 ± 2.8
AFP			0.636
≤ 8	34	14.3 ± 4.8
> 8	50	14.8 ± 5.2
Tumor number			0.003b
1	53	13.4 ± 5.0
> 1	31	16.6 ± 4.5
Extrahepatic metastasis			< 0.001c
No	10	13.5 ± 3.9
Yes	74	22.6 ± 6.6

^aP < 0.05.

^bP < 0.01.

^cP < 0.001.

BCLC: Barcelona Clinic Liver Cancer; CTC: Circulating tumor cells; AFP: Alpha-fetoprotein.

Table 3 Univariate analysis of disease-free survival time

Factors		Univariate analysis
		HR (95%CI)	Significance
CTC level	> 12.9	Reference1
	< 12.9	0.057 (0.016-0.201)	< 0.01b
Extrahepatic metastasis	No	Reference1
	Yes	4.953 (1.118-21.94)	0.031a
Tumor number	Multiple	Reference1
	Single	0.25 (0.096-0.65)	0.004b
Tumor diameter	> 5 cm	Reference1
	< 5 cm	0.44 (0.17-1.10)	0.0812
BCLC stage	A	Reference1
	B	2.604 (0.95-7.18)	0.064
	C	4.978 (1.001-24.75)	0.049a
Satellite	Yes	Reference1
	No	1.043 (0.6572-1.656)	0.858
Differentiation	High	Reference1
	Mediate	1.256 (0.1403-11.25)	0.458
	Low	2.213 (0.27-18.03)	0.838
Age	< 50	Reference1
	> 50	0.512 (0.1674-1.55)	0.237
AFP	> 400	Reference1
	< 400	0.57 (0.22-1.48)	0.25
Sex	Male	Reference1
	Female	0.55 (0.17-1.662)	0.287
Vascular invasion	Yes	Reference1
	No	1.132 (0.4-3.178)	0.814

^aP < 0.05.

^bP < 0.01.

¹Reference group.

CTC: Circulating tumor cells; BCLC: Barcelona Clinic Liver Cancer; AFP: Alpha-fetoprotein; HR: Hazard ratio; CI: Confidence interval.

Table 4 Multivariate analysis of disease-free survival time

Factors		Multivariate analysis
		HR (95%CI)	Significance
CTC level	< 12.9	0.04 (0.01-0.17)	< 0.001b
Tumor number	Single	0.19 (0.05-0.72)	0.015a
Extrahepatic metastasis		0.22 (0.03-1.58)	0.131
Diameter	< 5 cm	0.54 (0.08-3.58)	0.526
BCLC stage	B	1.43 (0.22-9.49)	0.709
	C	3.20 (0.31-33.09)	0.328

^aP < 0.05.

^bP < 0.001.

CTC: Circulating tumor cells; BCLC: Barcelona Clinic Liver Cancer; HR: Hazard ratio; CI: Confidence interval.