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中华肝脏外科手术学电子杂志 ›› 2019, Vol. 08 ›› Issue (06) : 497 -501. doi: 10.3877/cma.j.issn.2095-3232.2019.06.008

所属专题: 文献

临床研究

白血病抑制因子在肝癌肝移植受者复发预测中的作用
金平波1, 鲁迪1, 卓建勇1, 岑贝妮1, 谢海洋1, 郑树森1, 徐骁1,()   
  1. 1. 310000 杭州,浙江大学医学院附属第一医院肝胆胰外科 肝胰移植科
  • 收稿日期:2019-08-09 出版日期:2019-12-10
  • 通信作者: 徐骁
  • 基金资助:
    科技部科技重大专项基金(2017ZX10203205); 浙江省自然科学基金青年基金(LQ19H160030)

Role of leukemia inhibitory factor in predicting recurrence of hepatocellular carcinoma in recipients undergoing liver transplantation

Pingbo Jin1, Di Lu1, Jianyong Zhuo1, Beini Cen1, Haiyang Xie1, Shusen Zheng1, Xiao Xu1,()   

  1. 1. Department of Hepatobiliary Surgery, Department of Liver and Pancreas Transplantation, the First Affiliated Hospital of Zhejiang University, Hangzhou 310000, China
  • Received:2019-08-09 Published:2019-12-10
  • Corresponding author: Xiao Xu
  • About author:
    Corresponding author: Xu Xiao, Email:
引用本文:

金平波, 鲁迪, 卓建勇, 岑贝妮, 谢海洋, 郑树森, 徐骁. 白血病抑制因子在肝癌肝移植受者复发预测中的作用[J]. 中华肝脏外科手术学电子杂志, 2019, 08(06): 497-501.

Pingbo Jin, Di Lu, Jianyong Zhuo, Beini Cen, Haiyang Xie, Shusen Zheng, Xiao Xu. Role of leukemia inhibitory factor in predicting recurrence of hepatocellular carcinoma in recipients undergoing liver transplantation[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2019, 08(06): 497-501.

目的

探讨白血病抑制因子(LIF)在肝细胞癌(肝癌)肝移植受者复发预测中的作用。

方法

回顾性分析2009年8月至2015年12月浙江大学医学院附属第一医院诊治的105例肝癌肝移植受者临床资料。患者及其家属均签署知情同意书,符合医学伦理学规定。其中男100例,女5例;平均年龄(50±8)岁;中高-中分化43例,低分化62例;符合米兰标准患者22例。采用免疫组化芯片技术检测LIF表达。LIF在肝癌和癌旁组织中表达比较采用t检验,Cox多因素回归分析建立肝癌肝移植复发预测模型,采用受试者工作特征(ROC)曲线和DeLong检验评估模型预测价值。生存分析采用Kaplan-Meier法和Log-rank检验。

结果

LIF在肝癌组织中的表达强度为7.3±2.6,明显高于癌旁组织的5.0±2.4(t=6.670,P<0.05)。Cox多因素回归分析显示,肝癌组织LIF表达、lnAFP、血管侵犯是肝癌肝移植受者复发的独立危险因素(HR=1.178,1.177,2.280;P<0.05)。建立复发预测模型:0.164×LIF表达+ 0.163×lnAFP+ 0.824×血管侵犯。根据该模型将受者分为低危组及高危组。低危组受者1、3、5年生存率分别为82.7%,77.7%和73.6%,高危组相应为30.2%,17.3%和17.3%,低危组受者预后明显优于高危组(χ2=36.890,P<0.05)。本模型预测肝移植受者肝癌复发的ROC曲线下面积为0.849,预测效能明显强于米兰标准的0.626(Z=3.638,P<0.05)。

结论

肝癌组织中LIF表达增强,LIF表达是肝癌肝移植术后复发的独立危险因素,由此建立的模型能区分高危和低危复发患者,且较米兰标准更好地预测肝癌肝移植术后复发。

Objective

To investigate the role of leukemia inhibitory factor (LIF) in predicting the recurrence of hepatocellular carcinoma (HCC) in the recipients undergoing liver transplantation.

Methods

Clinical data of 105 HCC recipients undergoing liver transplantation in the First Affiliated Hospital of Zhejiang University from August 2009 to December 2015 were retrospectively analyzed. The informed consents of all patients and their family were obtained and the local ethical committee approval was received. Among the recipients, 100 were male and 5 female, aged (50±8) years on average. 43 patients were diagnosed with moderately-well or moderately-differentiated HCC and 62 cases of lowly-differentiated HCC. 22 patients met the Milan criteria. The LIF expression was detected by immunohistochemical tissue microarray and were statistically compared between HCC and para-cancerous tissues by t test. The model of predicting HCC recurrence after liver transplantation was established by Cox multivariate regression. The predictive value of the model was assessed by ROC curve and DeLong test. Survival analysis was performed by Kaplan-Meier method and Log-rank test.

Results

The LIF expression intensity in HCC tissues was 7.3±2.6, significantly higher than 5.0±2.4 in the para-cancerous tissues (t=6.670, P<0.05). Cox multivariate regression analysis indicated that LIF expression in HCC tissues, lnAFP and vascular invasion were the independent risk factors for HCC recurrence of the patients after liver transplantation (HR=1.178, 1.177, 2.280; P<0.05). A recurrence prediction model was established: 0.164×LIF expression level + 0.163×lnAFP + 0.824×vascular invasion. According to this model, all the recipients were divided into the low-risk and high-risk groups. The 1-, 3-, 5-year survival rates in low-risk group were 82.7%, 77.7%, 73.6%, significantly higher compared with 30.2%, 17.3%, 17.3% in high-risk group, respectively (χ2=36.890, P<0.05). The area under ROC curve of this model for predicting HCC recurrence in patients undergoing liver transplantation was 0.849, significantly better than 0.626 of the Milan criteria (Z=3.638, P<0.05).

Conclusions

LIF expression is up-regulated in HCC tissues. LIF expression is an independent risk factor for HCC recurrence in patients after liver transplantation. The corresponding model can tell patients with high-risk recurrence from those with low-risk recurrence. Compared with the Milan criteria, it can better predict HCC recurrence after liver transplantation.

表1 LIF表达与肝癌肝移植患者临床参数的关系( ±s
图1 本复发预测模型与米兰标准预测肝癌复发的ROC曲线
图2 低危组与高危组肝癌肝移植受者Kaplan-Meier生存曲线
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