Effect of FOXC2 on prognosis of liver transplant patients with primary liver cancer

doi:10.3877/cma.j.issn.2095-3232.2022.03.019

Abstract

Abstract:

Objective

To evaluate the effect of forkhead transcription factor C2 (FOXC2) on the clinical prognosis of patients with primary liver cancer (PLC) after liver transplantation.

Methods

Clinical data of 226 patients undergoing orthotopic liver transplantation in the 900^th Hospital of PLA Joint Logistics Support Force from January 2008 to January 2014 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. Among them, 159 patients were male and 67 female, aged from 38 to 73 years, with a median age of 54 years. The expression levels of FOXC2 mRNA and protein in the liver cancer tissues and adjacent tissues were determined by RT-PCR and Western blot. The relationship between FOXC2 expression and clinicopathological features of patients was analyzed. The value of FOXC2 in postoperative tumor recurrence and prognosis was evaluated. The relationship between the relative expression of FOXC2 mRNA and clinicopathological features of patients was analyzed by one-way ANOVA or t test. Survival analysis was performed by Kaplan-Meier method and Log-rank test. Prognostic factors were identified by Cox proportional hazards regression model.

Results

The relative expression level of FOXC2 mRNA in liver cancer tissues was 5.29±1.21, significantly higher than 3.70±0.79 in adjacent tissues (t=17.183, P<0.05). The relative expression of FOXC2 mRNA in liver cancer tissues was significantly correlated with HBsAg, preoperative AFP, maximum tumor diameter, tumor budding, tumor differentiation, tumor encapsulation and microvascular invasion (t=-4.341, -5.028, -4.461, -2.619, 3.919, 2.261, -2.107; P<0.05). In the high and low FOXC2 expression groups, the postoperative 3-year recurrence rates were 35.93% and 12.24%, and the postoperative 5-year survival rates were 58.59% and 86.73%, where significant differences were observed (χ²=23.849, 17.975; P<0.05). Cox multivariate analysis showed that expression level of FOXC2 mRNA was an independent influencing factor of tumor recurrence and overall survival of patients with PLC after liver transplantation (HR=0.197, 0.221; P<0.05).

Conclusions

FOXC2 is highly expressed in PLC. Patients with high expression of FOXC2 have high recurrence rate and poor prognosis after liver transplantation.

Key words: Carcinoma, hepatocellular, Liver transplantation, FOXC2, Microvascular invasion, Prognosis

Zhelong Jiang, Zhihong Wei, Junjie Du, Yi Jiang, Lizhi Lyu, Fang Yang. Effect of FOXC2 on prognosis of liver transplant patients with primary liver cancer[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2022, 11(03): 309-314.

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Figures/Tables 5

References 21

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参数		例数	FOXC2 mRNA相对表达量	统计值	P值
性别				t=1.147	<0.254
	男	159	5.36±1.12
	女	067	5.13±1.41
年龄				t=-0.038	-0.969
	<50岁	096	5.29±1.21
	≥50岁	130	5.29±1.22
HBsAg				t=-4.341	<0.001
	阴性	047	4.60±1.23
	阳性	179	5.47±1.15
肝硬化				t=1.805	<0.072
	否	127	5.42±1.29
	是	099	5.12±1.09
术前AFP				t=-5.028	<0.001
	<400 μg/L	033	4.35±1.06
	≥400 μg/L	193	5.45±1.17
术前Child-Pugh分级				F=0.362	<0.696
	A级	114	5.22±0.92
	B级	106	5.35±1.49
	C级	006	5.45±0.18
肿瘤最大直径				t=-4.461	<0.001
	<8 cm	109	4.93±1.36
	≥8 cm	117	5.63±0.95
卫星灶				t=-2.619	<0.009
	否	105	5.07±1.10
	有	121	5.48±1.28
米兰标准				t=0.629	<0.530
	不符合	106	5.34±1.13
	符合	120	5.24±1.29
肿瘤分化				t=3.919	<0.001
	低中分化	127	5.58±0.89
	高分化	099	4.92±1.46
肿瘤包膜				t=2.261	<0.025
	不完整	074	5.53±1.00
	完整	152	5.17±1.29
MVI				t=-2.107	<0.001
	阴性	077	5.05±1.20
	阳性	106	5.41±1.21

参数		例数	FOXC2 mRNA相对表达量	统计值	P值
性别				t=1.147	<0.254
	男	159	5.36±1.12
	女	067	5.13±1.41
年龄				t=-0.038	-0.969
	<50岁	096	5.29±1.21
	≥50岁	130	5.29±1.22
HBsAg				t=-4.341	<0.001
	阴性	047	4.60±1.23
	阳性	179	5.47±1.15
肝硬化				t=1.805	<0.072
	否	127	5.42±1.29
	是	099	5.12±1.09
术前AFP				t=-5.028	<0.001
	<400 μg/L	033	4.35±1.06
	≥400 μg/L	193	5.45±1.17
术前Child-Pugh分级				F=0.362	<0.696
	A级	114	5.22±0.92
	B级	106	5.35±1.49
	C级	006	5.45±0.18
肿瘤最大直径				t=-4.461	<0.001
	<8 cm	109	4.93±1.36
	≥8 cm	117	5.63±0.95
卫星灶				t=-2.619	<0.009
	否	105	5.07±1.10
	有	121	5.48±1.28
米兰标准				t=0.629	<0.530
	不符合	106	5.34±1.13
	符合	120	5.24±1.29
肿瘤分化				t=3.919	<0.001
	低中分化	127	5.58±0.89
	高分化	099	4.92±1.46
肿瘤包膜				t=2.261	<0.025
	不完整	074	5.53±1.00
	完整	152	5.17±1.29
MVI				t=-2.107	<0.001
	阴性	077	5.05±1.20
	阳性	106	5.41±1.21

变量	b	Wald χ²	P	HR	95%CI
肿瘤直径<8 cm	0.652	5.713	<0.017	0.521	0.305~0.8890
卫星灶阳性	0.436	0.604	<0.031	1.588	1.042~2.2400
肿瘤中低分化	0.737	7.405	<0.007	2.090	1.229~3.5540
肿瘤包膜完整	0.554	0.035	<0.012	0.947	0.536~1.6720
MVI阳性	2.060	21.995	<0.001	7.845	3.314~18.569
FOXC2 mRNA< 5.29	1.623	22.871	<0.001	0.197	0.101~0.3840

变量	b	Wald χ²	P	HR	95%CI
肿瘤直径<8 cm	0.652	5.713	<0.017	0.521	0.305~0.8890
卫星灶阳性	0.436	0.604	<0.031	1.588	1.042~2.2400
肿瘤中低分化	0.737	7.405	<0.007	2.090	1.229~3.5540
肿瘤包膜完整	0.554	0.035	<0.012	0.947	0.536~1.6720
MVI阳性	2.060	21.995	<0.001	7.845	3.314~18.569
FOXC2 mRNA< 5.29	1.623	22.871	<0.001	0.197	0.101~0.3840

变量	b	Wald χ²	P	HR	95%CI
肿瘤直径<8 cm	0.591	4.072	<0.044	0.554	0.312~0.9830
肿瘤中低分化	0.764	6.771	<0.009	2.147	1.207~3.8170
MVI阳性	2.035	18.030	<0.001	7.649	2.991~19.566
FOXC2 mRNA< 5.29	1.511	17.851	<0.001	0.221	0.110~0.4450

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