Methylation of Dickkopf-3 as a prognostic factor in cirrhosis-related hepatocellular carcinoma

Table 1 DKK methylation frequencies in HCC and NCL tissue samples

	Positive (PMR > 1%)	Negative (PMR ≤ 1%)	P
DKK1
HCC	14	36	0.6484
NCL	12	38
DKK2
HCC	21	29	0.0076
NCL	8	42
DKK3
HCC	27	23	< 0.0001
NCL	2	48

DKK: Dickkopf; HCC: Hepatocellular carcinoma; PMR: Percent of methylated reference; NCL: Noncancerous cirrhotic liver.

Table 2 Correlation between DKK3 methylation and clinicopathological characteristics

	Positive (PMR > 1%)	Negative (PMR ≤ 1%)	P
Total	27	23
Sex
Male (n = 43)	23	20
Female (n = 7)	4	3	1.000
Age (yr)
≤ 55 (n = 28)	14	14
> 55 (n = 22)	13	9	0.5773
Virus status
Positive (n = 44)1	22	22
Negative (n = 6)	3	3	1.000
AFP (ng/mL)
≤ 400 (n = 30)	17	13
> 400 (n = 20)	11	9	1.000
Tumor size (cm)
≤ 5.0 (n = 19)	9	10
> 5.0 (n = 31)	18	13	0.5630
Number of tumor
Single (n = 31)	13	18
Multiple (n = 19)	14	5	0.0417
Portal vein invasion
Positive (n = 17)	9	8
Negative (n = 33)	18	15	1.000

¹Including 42 cases of hepatitis B virus and 2 cases of hepatitis C virus carriers. AFP: α-fetoprotein.

Table 3 Cox regression model of progression-free survival

	Univariate analysis			Multivariate analysis1
	RR	95% CI	P	RR	95% CI	P
Tumor size (cm)
> 5.0	3.653	1.085-12.304	0.036	3.345	1.312-8.526	0.011
≤ 5.0	1			1
Portal vein invasion
Positive	2.657	1.023-6.900	0.045	3.188	1.294-7.852	0.012
Negative	1			1
DKK3 methylation
Positive (PMR > 1%)	2.370	0.965-5.823	0.060	2.527	1.063-6.008	0.036
Negative (PMR ≤ 1%)	1			1
AFP (ng/mL)
> 400	1.829	0.759-4.409	0.179			-
≤ 400	1
Age (yr)
> 55	1.552	0.569-4.234	0.391			-
≤ 55	1
Number of tumor
Multiple	0.922	0.280-3.036	0.893			-
Single	1

¹Only the variables with P values less than 0.05 are included in the equation. RR: Relative risk.