KIAA1199 overexpression is associated with abnormal expression of EMT markers and is a novel independent prognostic biomarker for hepatocellular carcinoma

Figures & data

Table 1 Differential expression of KIAA1199 in HCC tissues and corresponding paracarcinoma tissues (n=178)

Tissue	KIAA1199 expression		P-value
	Low (%)	High (%)
HCC tissues	46 (25.8)	132 (74.2)	0.01
Paracarcinoma tissues	112 (62.9)	66 (37.1)

Abbreviation: HCC, hepatocellular carcinoma.

Figure 1 Immunohistochemical staining for KIAA1199, E-cadherin, N-cadherin and vimentin. Magnification 400×.

Notes: (A1) Negative KIAA1199 expression. (A2) Positive KIAA1199 expression. (B1) Positive E-cadherin expression. (B2) Negative E-cadherin expression. (C1) Negative N-cadherin expression. (C2) Positive N-cadherin expression. (D1) Negative vimentin expression. (D2) Positive vimentin expression. KIAA1199 is principally localized in cytoplasm of tumor cells; E-cadherin is mainly localized in the cytomembrane of cells; vimentin is mainly localized in the cytoplasm of tumor cells; N-cadherin is localized in the cytoplasm and on the membrane of the tumor cells.

Figure 2 qPCR analysis of KIAA1199 expression in 20 pairs of HCC tissues and matched adjacent normal tissues.

Note: ****P<0.05.

Figure 3 (A) Representative images of KIAA1199 protein expression in HCC tissues and paired normal tissues from three patients. (B) Western blot analysis of KIAA1199 expression in 20 pairs of HCC tissues and matched adjacent normal tissues.

Note: ****P<0.05.
Abbreviation: HCC, hepatocellular carcinoma.

Table 2 Correlations of KIAA1199 expression with E-cadherin, N-cadherin and vimentin in HCC

Immunoreactivity	KIAA1199 expression		R-value	P-value
	Low	High
E-cadherin expression
Low	24	102	−0.242	0.001
High	22	30
N-cadherin expression
Low	27	23	0.402	<0.001
High	19	109
Vimentin expression
Low	18	15	0.313	<0.001
High	28	117

Abbreviation: HCC, hepatocellular carcinoma.

Table 3 KIAA1199 expression status in relation to clinicopathologic features in 178 HCC patients

Parameters	Case number	KIAA1199 expression		χ^2	P-value
		Low	High
Age (years)
≤60	130	30	100	1.924	0.165
>60	48	16	32
Gender
Male	108	27	81	0.141	0.707
Female	69	19	50
Tumor size (cm)
≤5	63	14	49	0.667	0.414
>5	115	32	83
Tumor nodule number
Single	136	37	99	0.559	0.455
Multiple	42	9	33
Vascular invasion
Yes	88	8	80	25.485	<0.05
No	90	38	52
Tumor capsula
Absent	72	20	52	0.236	0.627
Present	106	26	80
Edmondson grade
I–II	87	35	52	18.381	<0.05
III–IV	91	11	80
Cirrhosis
Absent	72	17	55	0.314	0.575
Present	106	29	77
lHBeAg status
Positive	126	29	97	1.798	0.180
Negative	52	17	35
Child-Pugh grade
A	168	43	125	0.096	0.757
B	10	3	7
TNM stage
I–II	109	39	70	14.489	<0.05
III–IV	69	7	62
AFP (ng/mL), U/mL
≤20	37	28	9	60.526	<0.05
>20	141	18	123

Abbreviations: AFP, alpha-fetoprotein; HCC, hepatocellular carcinoma.

Figure 4 Kaplan-Meier analysis of DFS and OS in patients with HCC according to KIAA1199 staining.

Note: Patients with high KIAA1199 expression had a shorter OS and DFS than did those with low KIAA1199 expression (n=178; P<0.05; log rank test).
Abbreviations: DFS, disease-free survival; HCC, hepatocellular carcinoma; OS, overall survival.

Table 4 Univariate and multivariate analysis of factors associated with OS and DFS

Parameter	OS			DFS
	HR	95% CI	P-value	HR	95% CI	P-value
Univariate analysis
Age (≤60 vs >60 years)	0.956	0.832–1.029	0.866	0.865	0.726–1.328	0.863
Gender (male vs female)	0.865	0.647–1.329	0.876	0.843	0.756–1.312	0.722
Tumor size (≤5 vs >5 cm)	0.952	0.683–1.464	0.812	0.733	0.697–1.527	0.912
Tumor nodule number (single vs multiple)	1.982	0.926–2.007	0.125	1.731	0.936–1.982	0.163
Vascular invasion (no vs yes)	4.357	3.874–8.543	<0.001	5.374	4.387–9.614	<0.001
Tumor capsula (absent vs present)	0.613	0.432–0.926	0.079	0.567	0.432–0.946	0.081
Edmondson grade (I–II vs III–IV)	2.957	1.852–4.237	<0.001	3.327	1.928–3.658	<0.001
Cirrhosis (absent vs present)	1.169	0.829–2.211	0.521	1.087	0.810–1.921	0.832
HBeAg status (positive vs negative)	0.936	0.689–1.431	0.897	0.811	0.481–1.235	0.336
Child-Pugh grade (A vs B)	1.231	0.753–1.564	0.877	1.012	0.789–1.515	0.802
TNM stage (I–II vs III–IV)	2.569	1.556–3.283	<0.001	2.693	1.894–3.324	<0.001
AFP (≤20 vs >20 U/mL)	2.322	1.274–3.285	0.018	2.153	1.201–2.894	0.043
KIAA1199 expression (high vs low)	2.342	1.923–2.888	<0.001	2.796	1.568–3.368	<0.001
Multivariate analysis
Vascular invasion (no vs yes)	7.151	5.534–9.427	<0.001	15.635	8.007–27.832	<0.001
Edmondson grade (I–II vs III–IV)	4.447	2.957–5.232	<0.001	3.987	2.988–4.958	<0.001
TNM stage (I–II vs III–IV)	3.596	2.589–4.129	<0.001	5.351	3.110–7.654	<0.001
AFP (≤20 vs >20 U/mL)	2.754	1.524–3.153	0.014	1.654	1.740–2.845	0.023
KIAA1199 expression (low vs high)	4.835	2.655–6.229	<0.001	4.223	2.552–5.756	<0.001

Abbreviations: AFP, alpha-fetoprotein; DFS, disease-free survival; HCC, hepatocellular carcinoma; OS, overall survival.