Loss of Wnt5a and Ror2 protein in hepatocellular carcinoma associated with poor prognosis

Table 1 The relationship between receptor 2 expression and clinicopathological features in hepatocellular carcinomas

Variables	n	Ror2 immunoreactivity		P
		Low	High
Gender				0.890
Male	77	56	21
Female	8	6	2
Age (yr)				0.725
< 53 (median)	38	27	11
≥ 53	47	35	12
Serum AFP level (μg/L)				< 0.001
< 30	30	14	16
≥ 30	55	48	7
HBsAg				0.862
Positive	73	53	20
Negative	12	9	3
Tumor size (cm)				0.116
≤ 2	3	1	2
> 2	82	61	21
Histological grade				0.090
Well differentiated	9	7	2
Moderately differentiated	60	40	20
Poorly differentiated	16	15	1
Liver cirrhosis				0.553
Present	56	42	14
Absent	29	20	9
T classification				< 0.001
T1	3	1	2
T2	30	14	16
T3	40	36	4
T4	12	11	1
Total	85	62	23

AFP: α-fetoprotein; HBsAg: Hepatitis B surface antigen; Ror2: Receptor tyrosine kinase-like orphan receptor 2.

Table 2 Correlation between the expression levels of Wnt member 5a, receptor 2 and β-catenin

	Wnt5a				β-catenin
Variable	n	Low	High	P-value	n	A	P-value
Ror2
Low	62	54	8	< 0.001	15	47	0.014
High	23	11	12		12	11
β-catenin
N	27	16	11	0.019
A	58	48	10

N: Normal membranous staining; A: Abnormal non-membranous staining; Wnt5a: Wnt member 5a; Ror2: receptor tyrosine kinase-like orphan receptor 2.

Table 3 Univariate Cox and multivariate Cox regression analysis overall survival

Covariate	P-value	Risk ratio	95% CI
Univariate
Sex (male, female)	0.130	0.482	0.187-1.240
Age (< 53 yr, ≥ 53 yr)	0.166	0.640	0.341-1.203
Serum AFP level (< 30 μg/L, ≥ 30 μg/L)	0.036a	2.162	1.051-4.449
HBsAg (positive, negative)	0.506	1.621	0.390-6.732
Tumor size ( ≤ 2 cm, > 2 cm)	0.467	2.089	0.286-15.239
Histological grade (well, moderately, poorly differentiated)	0.268	1.388	0.777-2.482
Liver cirrhosis (present, absent)	0.738	1.123	0.568-6.732
T classification (T1-T4)	< 0.001a	2.339	1.487-3.679
Wnt5a (low, high)	0.024a	3.288	1.167-9.263
Ror2 (low, high)	0.011a	0.323	0.134-0.774
β-catenin ( normal, abnormal)	0.052a	1.966	0.995-3.885
Ki-67 (mitosis ≤ 10%, > 10%)	0.273	1.479	0.734-2.981
Multivariate
Sex (male, female)	0.017a	0.240	0.074-0.776
Age (< 53 yr, ≥ 53 yr)	0.075	0.538	0.272-1.065
Serum AFP level (< 30 μg/L, ≥ 30 μg/L)	0.343	1.476	0.661-3.296
HBsAg (positive, negative)	0.515	1.731	0.332-9.026
Tumor size ( ≤ 2 cm, > 2 cm)	0.711	1.535	0.159-14.827
Histological grade (well, moderately, poorly differentiated)	0.298	1.462	0.715-2.993
Liver cirrhosis (present, absent)	0.858	0.928	0.408-2.111
T classification (T1-T4)	0.001a	2.119	1.347-3.336
Wnt5a (low, high)	0.020a	0.288	0.101-0.824
Ror2 (low, high)	0.144	0.509	0.205-1.259
β-catenin ( normal, abnormal)	0.013a	3.233	1.286-8.130
Ki-67 (mitosis ≤ 10%, > 10%)	0.494	0.839	0.507-1.387

^aP < 0.05 vs over survival. AFP: α-fetoprotein; HBsAg: Hepatitis B surface antigen; Wnt5a: Wnt member 5a; Ror2: Receptor tyrosine kinase-like orphan receptor 2