Cullin 4A is associated with epithelial to mesenchymal transition and poor prognosis in perihilar cholangiocarcinoma

Table 1 Correlation between cullin 4A expression and clinicopathologic parameters of perihilar cholangiocarcinoma

Parameter	n	CUL4A IHC score	P value
Age (yr)			0.902
< 65	54	4.07 ± 2.46
≥ 65	24	3.99 ± 2.47
Gender			0.606
Male	45	3.92 ± 2.34
Female	33	4.21 ± 2.62
Tumour size (cm)			0.330
< 3	36	3.75 ± 2.55
≥ 3	42	4.30 ± 2.36
Differentiation grade			< 0.001
Well + moderate	66	3.56 ± 2.30
Poor + undifferentiated	12	6.68 ± 1.24
T stage			0.001
T1 + T2	63	3.62 ± 2.34
T3 + T4	15	5.81 ± 2.12
N stage			< 0.001
N0	64	3.35 ± 2.08
N1 + N2	14	7.21 ± 1.13
M stage			0.980
M0	76	4.04 ± 2.46
M1	2	4.00 ± 2.83
TNM stage			< 0.001
I + II	54	3.14 ± 2.03
III + IV	24	6.08 ± 2.07

IHC: Immunohistochemistry; CUL4A: Cullin 4A.

Table 2 Multivariate analysis of clinicopathologic features for overall survival and progression-free survival of perihilar cholangiocarcinoma patients

Parameter	Overall survival			Progression-free survival
	HR	95%CI	P value	HR	95%CI	P value
Univariate analysis
Age: ≥ 65 yr vs < 65 yr	1.218	0.676-2.193	0.512	1.097	0.616-1.954	0.753
Gender: male vs female	1.003	0.569-1.767	0.993	0.931	0.538-1.610	0.798
Differentiation: well + moderate vs poor + undifferentiated	0.432	0.171-1.092	0.076	0.461	0.196-1.083	0.075
Tumour size: ≥ 3 cm vs < 3 cm	1.049	0.598-1.839	0.869	1.008	0.586-1.733	0.977
T stage: (T3 + T4) vs (T1 + T2)	2.181	1.129-4.213	0.020	1.871	0.977-3.583	0.059
N stage: N1 + N2 vs N0	3.120	1.613-6.036	0.001	2.917	1.515-5.619	0.001
M stage: M1 vs M0	4.761	0.54-38.170	0.142	2.766	0.363-21.092	0.326
TNM stage: (III + IV) vs (I + II)	3.001	1.671-5.387	< 0.001	2.729	1.538-4.842	0.001
CUL4A: high vs low	2.823	1.577-5.053	< 0.001	2.964	1.691-5.196	< 0.001
Multivariate analysis
T stage: (T3 + T4) vs (T1 + T2)	0.811	0.271-2.424	0.708	-	-	-
N stage: N1 + N2 vs N0	0.969	0.305-3.081	0.957	1.106	0.428-2.857	0.836
TNM stage: (III + IV) vs (I + II)	2.483	0.632-9.752	0.193	1.699	0.735-3.928	0.215
CUL4A: high vs low	2.117	1.086-4.125	0.028	2.248	1.240-4.446	0.009