CNTN-1和VEGF-C表达水平与肝癌肝移植术后复发转移及预后的关系

曹毅; 吕立志; 江艺; 潘凡; 杨和君

doi:10.3969/j.issn.1674-7445.2017.02.012

CNTN-1和VEGF-C表达水平与肝癌肝移植术后复发转移及预后的关系

doi: 10.3969/j.issn.1674-7445.2017.02.012

350025 福州，福建医科大学福总临床医学院（曹毅）；南京军区福州总医院肝胆外科（吕立志、江艺、潘凡、杨和君）

基金项目:

福建省自然科学基金重点项目 2014Y0034

详细信息

通讯作者:
吕立志, Email:fzzyllz@qq.com

中图分类号: R617, R735.7
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- 被引次数: 0
出版历程
- 收稿日期: 2016-11-20
- 网络出版日期: 2021-01-19
- 刊出日期: 2017-03-15

Relationship between CNTN-1 and VEGF-C expression levels and recurrence, metastasis and prognosis of hepatocellular carcinoma patients after liver transplantation

Clinical Medical School, Fuzhou General Hospital of Nanjing Military Area Command, Fujian Medical University, Fuzhou 350025, China

More Information

Corresponding author: Lyu Lizhi, Email:fzzyllz@qq.com

摘要

摘要: 目的探讨接触蛋白（CNTN）-1和血管内皮生长因子（VEGF）-C的表达与肝细胞癌（肝癌）肝移植患者术后复发转移及预后的关系。方法收集105例行经典原位肝移植治疗的原发性肝癌患者的临床资料及病理标本。采用免疫组织化学染色法检测肝癌组织和相应的癌旁肝组织中CNTN-1和VEGF-C的表达情况，并对其与临床病理特征及术后复发转移及预后的关系进行统计学分析。结果肝癌组织的CNTN-1与VEGF-C高表达率分别为46.7%和39.0%，在癌旁组织分别为11.4%和19.0%，两者比较差异均有统计学意义（均为P＜0.05）。Spearman相关分析显示CNTN-1与VEGF-C的表达呈正相关（P < 0.005）。χ²检验显示，CNTN-1蛋白的表达与甲胎蛋白（AFP）高低（P=0.017），肿瘤、淋巴、转移（TNM）分期（P＜0.001）呈正相关，与分化程度呈负相关（P＜0.001）；VEGF-C高表达与TNM分期呈正相关（P＜0.001）。Cox多因素分析显示，患者总存活率与性别、AFP、肿瘤分化程度、微血管侵犯、肿瘤直径、CNTN-1高表达有显著相关性（P＜0.05~0.001）；患者无复发存活率与TNM分期、包膜完整性、CNTN-1高表达相关（P＜0.05~0.001）。Kaplan-Meier分析显示CNTN-1高表达患者与CNTN-1低表达患者的术后总生存曲线以及术后无复发生存曲线差异有统计学意义（均为P < 0.01），VEGF-C高表达患者与低表达患者仅在术后无复发生存曲线差异有统计学意义（P=0.005）。结论 CNTN-1蛋白水平在肝癌组织中高表达，且与VEGF-C的表达相关，与肝癌肝移植术后复发转移有关，影响肝癌肝移植患者预后。
- 肝细胞癌 /
- 肝移植 /
- 接触蛋白-1 /
- 血管内皮生长因子-C /
- 微血管侵犯 /
- 包膜 /
- 无复发生存 /
- 预后
Abstract: Objective To investigate the relationship between contactin (CNTN)-1 and vascular endothelial growth factor (VEGF)-C expression levels and the recurrence, metastasis and prognosis of hepatocellular carcinoma (HCC) patients after liver transplantation. Methods Clinical data and pathological specimen of 105 patients diagnosed with primary HCC undergoing orthotopic liver transplantation were collected. The expression levels of CNTN-1 and VEGF-C in the cancerous and para-cancerous liver tissues were quantitatively measured by immunohistochemical staining. The relationship between the CNTN-1 and VEGF-C expression levels and clinicopathological characteristics, postoperative recurrence, metastasis and prognosis was statistically analyzed. Results The high expression rate of CNTN-1 and VEGF-C in liver cancerous tissues was 46.7% and 39.0%, significantly higher compared with 11.4% and 19.0% in the para-cancerous tissues (both P < 0.05). Spearman correlation analysis revealed that the expression level of CNTN-1 was positively correlated with that of VEGF-C (P < 0.005). χ² test demonstrated that the expression of CNTN-1 protein was positively correlated with the level of alpha fetoprotein (AFP) (P=0.017), tumor, node, metastasis (TNM) staging (all P < 0.001), and negatively correlated with the degree of differentiation (P < 0.001). High expression of VEGF-C was positively correlated with TNM staging (P < 0.001). Cox multivariate analysis revealed that overall survival rate was significantly correlated with gender, AFP, degree of tumor differentiation, microvascular invasion, tumor diameter and high expression of CNTN-1 (P < 0.05-0.001). The recurrence-free survival was correlated with TNM staging, envelope integrity and high CNTN-1 expression (P < 0.05-0.001). Kaplan-Meier survival analysis revealed that postoperative overall survival curve and recurrence-free survival curve significantly differed between patients with high and low expression levels of CNTN-1 (both P < 0.01). Recurrence-free survival curve significantly differed between patients with high and low expression levels of VEGF-C (P=0.005). Conclusions CNTN-1 protein is highly expressed in HCC tissues and correlated with the expression of VEGF-C. It is associated with postoperative recurrence and metastasis of HCC after liver transplantation and affects the clinical prognosis of patients.
- Hepatocellular carcinoma /
- Liver transplantation /
- Contactin-1 /
- Vascular endothelial growth factor-C /
- Microvascular invasion /
- Envelope /
- Recurrence-free survival /
- Prognosis

HTML全文

图 1 肝癌组织中VEGF-C和CNTN-1的免疫组织化学染色

A、B图均为VEGF-C蛋白阳性表达，肝癌细胞胞浆内可见棕褐色颗粒（A图，×200；B图，×400）；C、D图均为CNTN1蛋白阳性表达，肝癌细胞胞浆内可见棕褐色颗粒（C图，×200；D图，×400)

Figure 1. Immunohistochemical staining for VEGF-C and CNTN-1 in HCC tissue

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图 2 肝癌组织CNTN-1、VEGF-C表达与肝癌患者肝移植术后无复发存活率及总存活率的关系

Figure 2. Relationship between CNTN-1 and VEGF-C expression in HCC tissue and relapse free survival rate and overall survival rate of patients with HCC after liver transplantation

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表 1 肝癌组织CNTN-1/VEGF的表达与患者临床病理学指标的关系

Table 1. Association between CNTN-1/VEGF-C expression in HCC tissue and index of patients[n(%)]

特征	n	CNTN-1		P值	VEGF-C		P值
特征	n	低表达	高表达	P值	低表达	高表达	P值
年龄（岁）
≤55	71	36(64)	35(71)	0.435	44(69)	27(66)	0.757
＞55	34	20(36)	14(29)		20(31)	14(34)
性别
男	95	52 (93)	43(88)	0.373	60 (94)	35(85)	0.153
女	10	4(7)	6(12)		4(6)	6 (15)
肿瘤分化程度
高、中分化	65	45(80)	20 (41)	< 0.001	44(69)	21 (51)	0.071
低分化	40	11(20)	29 (59)		20(31)	20(49)
血清AFP水平
≤400 μg/ L	58	37(66)	21(43)	0.017	36(56)	22(54)	0.794
> 400 μg/ L	47	19(34)	28(57)		28(44)	19(46)
微血管侵犯
否	59	36 (64)	23(47)	0.074	38 (59)	21(51)	0.411
是	46	20(36)	26 (53)		26 (41)	20 (49)
TNM分级
Ⅰ/Ⅱ	69	47 (84)	22(45)	< 0.001	50 (78)	19(46)	0.001
Ⅲa	36	9(16)	27 (55)		14 (22)	22 (54)
包膜完整性
否	34	14(25)	20(41)	0.084	21 (33)	13(32)	0.906
是	71	42(75)	29(60)		43(67)	28 (68)
肿瘤直径
≤5 cm	53	29(52)	24 (49)	0.774	35(55)	18(44)	0.281
> 5 cm	52	27(48)	25(51)		29 (45)	23(56)
肿瘤复发
是	42	11 (20)	31(63)	< 0.001	20(31)	22 (54)	0.022
否	63	45 (80)	18(37)		44(69)	19(46)
预后
死亡	62	20 (36)	42(86)	< 0.001	36(56)	26 (63)	0.466
存活	43	36 (64)	7(14)		28 (44)	15(37)

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参考文献(17)

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