HBV感染相关肝癌肝移植术后复发的预测模型

doi:10.3760/cma.j.cn371439-20210121-00143

摘要/Abstract

摘要： 目的探讨乙型肝炎病毒(HBV)感染相关肝细胞癌(HCC)患者行肝移植术后复发的危险因素,并进一步构建预测模型。方法回顾性分析2015年1月至2020年5月河北北方学院附属第一医院诊治的106例行肝移植HCC患者的临床资料。采用χ ²检验进行HCC复发影响因素的单因素分析,logistic回归分析进行HCC复发影响因素的多因素分析,根据筛选的危险因素构建HCC复发的预测模型,并采用受试者工作特征(ROC)曲线对预测模型进行评价。结果 106例肝移植HCC患者复发23例,复发率为21.70%;死亡20例。肿瘤分化程度(χ ²=6.066,P=0.014)、肿瘤最大径(χ ²=4.916,P=0.027)、有无包膜侵犯(χ ²=5.543,P=0.019)、术前甲胎蛋白(AFP)(χ ²=5.458,P=0.019)、HBV-DNA(χ ²=5.446,P=0.020)、中性粒细胞淋巴细胞比值(NLR)(χ ²=12.161,P<0.001)、miR-424(χ ²=4.400,P=0.036)、染色质域解旋酶DNA结合蛋白8(CHD8)(χ ²=10.561,P=0.001)、T-钙黏蛋白(T-cad)(χ ²=48.723,P<0.001)、层粘连蛋白(LN)(χ ²=18.506,P<0.001)、肝细胞生长因子(HGF)表达(χ ²=11.178,P=0.001)与HCC复发有关。多因素logistic回归分析显示,肿瘤最大径≥6.5 cm(OR=1.69,95%CI为1.25~3.17,P=0.002)、术前AFP>400 ng/ml(OR=1.38,95%CI为1.09~1.92,P=0.038)、CHD8阳性(OR=0.77,95%CI为0.52~0.89,P=0.021)、T-cad阳性(OR=0.84,95%CI为0.68~0.92,P=0.006)、LN阳性(OR=1.22,95%CI为1.03~1.50,P=0.013)是HCC复发的危险因素。根据logistic回归分析结果构建函数模型logit(P)=0.262+0.523X₁+0.326X₂-0.259X₃-0.286X₄+0.203X₅,其中X₁、X₂、X₃、X₄、X₅分别为肿瘤最大径、AFP、CHD8、T-cad、LN。ROC曲线分析显示,其预测HCC复发的曲线下面积为0.849(95%CI为0.763~0.894,P<0.001),准确率为83.02%,敏感性为86.96%,特异性为81.93%,临界值为0.736。由logit(P)函数模型可知,P=1/(1+e ^- ^Y),其中Y=0.262+0.523X₁+0.326X₂-0.259X₃-0.286X₄+0.203X₅。随机抽取1例患者,根据其临床资料,经计算P=0.564,小于临界值0.736,可认为在准确率为83.02%的情况下,该患者不会出现HCC复发。结论肿瘤最大径、术前AFP、CHD8、T-cad、LN表达状况与肝移植后HCC复发有关,据此构建的预测模型可有效预测HCC复发的风险。

关键词: 癌, 肝细胞, 肝移植术, 甲胎蛋白, 肿瘤直径

Abstract: Objective To investigate the risk factors for recurrence after liver transplantation in patients with hepatitis B virus (HBV) infection-related hepatocellular carcinoma (HCC), and to further construct a predictive model. Methods The clinical data of 106 patients with HCC undergoing liver transplantation in the First Affiliated Hospital of Hebei North University from January 2015 to May 2020 were retrospec-tively analyzed. The χ ² test was used to analyze the factors influencing HCC recurrence, and multivariate logistic regression was used to analyze the influencing factors of HCC recurrence. According to the selected risk factors, the predictive model of HCC recurrence was constructed, and the receiver operating characteristic (ROC) curve was used to evaluate the predictive model. Results Of the 106 HCC patients, 23 had recurrence, with a recurrence rate of 21.70%, and 20 died. Tumor differentiation (χ ²=6.066, P=0.014), maximum tumor diameter (χ ²=4.916, P=0.027), with or without envelope invasion (χ ²=5.543, P=0.019), preoperative alpha fetoprotein (AFP) (χ ²=5.458, P=0.019), HBV-DNA (χ ²=5.446, P=0.020), neutrophil lymphocyte ratio (NLR) (χ ²=12.161, P<0.001), the expressions of miR-424 (χ ²=4.400, P=0.036), chromodomain helicase DNA-binding protein 8 (CHD8) (χ ²=10.561, P=0.001), T-cadherin (T-cad) (χ ²=48.723, P<0.001), laminin (LN) (χ ²=18.506, P<0.001) and hepatocyte growth factor (HGF) (χ ²=11.178, P=0.001) were related to the recurrence of HCC. Multivariate logistic regression analysis showed that the maximum tumor diameter≥6.5 cm (OR=1.69, 95%CI: 1.25-3.17, P=0.002), preoperative AFP>400 ng/ml (OR=1.38, 95%CI: 1.09-1.92, P=0.038), positive CHD8 (OR=0.77, 95%CI: 0.52-0.89, P=0.021), positive T-cad (OR=0.84, 95%CI: 0.68-0.92, P=0.006), positive LN (OR=1.22, 95%CI: 1.03-1.50, P=0.013) were the risk factors of HCC recurrence. According to the results of logistic analysis, the regression equation logit(P)=0.262+0.523X₁+0.326X₂-0.259X₃-0.286X₄+0.203X₅ was constructed, where X₁, X₂, X₃, X₄, X₅ were the maximum tumor diameter, AFP, CHD8, T-cad and LN. ROC curve analysis showed that the area under the curve for predicting HCC recurrence was 0.849 (95%CI: 0.763-0.894, P<0.001), the accuracy rate was 83.02%, the sensitivity was 86.96%, the specificity was 81.93%, and the cut-off value was 0.736. According to the logit(P) function model, P=1/(1+e ^- ^Y), where Y=0.262+0.523X₁+0.326X₂-0.259X₃-0.286X₄+0.203X₅. One patient was randomly selected. According to his clinical data, P=0.564, which was less than the cut-off value (0.736). It could be considered that this patient would not have HCC recurrence with an accuracy rate of 83.02%. Conclusion Tumor maximum diameter, preoperative AFP, CHD8, T-cad, LN expression are related to the recurrence of HCC after liver transplantation. The prediction model constructed based on this can effectively predict the risk of HCC recurrence.

Key words: Carcinoma, hepatocellular, Liver transplantation, Alpha-fetoprotein, Tumor diameter

白雪, 孟庆庆, 陈勇, 李静. HBV感染相关肝癌肝移植术后复发的预测模型[J]. 国际肿瘤学杂志, 2021, 48(12): 723-728.

Bai Xue, Meng Qingqing, Chen Yong1, Li Jing. Prediction model of HBV infection-related liver cancer recurrence after liver transplantation[J]. Journal of International Oncology, 2021, 48(12): 723-728.

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变量	β值	Wald 值	OR值(95%CI)	P值
常量	0.262	4.589	1.30(1.06~1.67)	0.008
分化程度低分化	0.132	3.573	1.14(0.52~1.63)	0.085
肿瘤最大径≥6.5 cm	0.523	4.769	1.69(1.25~3.17)	0.002
有包膜侵犯	0.235	2.833	1.26(0.73~1.84)	0.178
术前AFP>400 ng/ml	0.326	4.028	1.38(1.09~1.92)	0.038
HBV-DNA≥500 U/ml	0.141	2.892	1.15(0.59~1.76)	0.177
NLR≥3.5	0.158	3.665	1.17(0.61~2.08)	0.083
miR-424阳性	-0.184	2.306	0.83(0.77~1.59)	0.238
CHD8阳性	-0.259	4.323	0.77(0.52~0.89)	0.021
T-cad阳性	-0.286	4.602	0.84(0.68~0.92)	0.006
LN阳性	0.203	4.538	1.22(1.03~1.50)	0.013
HGF阳性	0.169	3.135	1.18(0.62~1.72)	0.126