血清异常凝血酶原预测肝癌肝移植术后肿瘤复发的价值研究

Study on the value of serum des-γ-carboxy prothrombin in predicting hepatocellular carcinoma recurrence after liver transplantation

目的探究血清异常凝血酶原(DCP)对肝癌肝移植术后复发的临床预测价值。方法回顾性入组2016年10月至2018年12月在复旦大学附属中山医院接受肝移植手术的肝细胞肝癌患者资料115例,用受试者工作特征曲线分析、Mann-Whitney U检验、Kaplan-Meier法、Log-Rank检验、χ^2检验、单因素回归、多因素Cox回归分析等统计学方法探究DCP预测肝癌肝移植术后肿瘤复发的价值及其与临床病理特征的相关性。结果肝移植术后复发人群术前血清DCP水平显著高于未复发人群(P<0.001);用受试者工作特征曲线分析确定术前DCP预测复发的最佳界值为200 mAU/ml,灵敏度为87.90%,特异度为57.30%,约登指数为0.452,受试者工作特征曲线下面积为0.726;以此界值分组的生存分析结果显示术前DCP≥200 mAU/ml的患者拥有更高的复发概率(P<0.001),且在进一步亚组生存分析中,在甲胎蛋白阴性亚组、累计肿瘤直径≤9 cm亚组和符合米兰标准亚组中,术前DCP≥200 mAU/ml患者相比其他患者拥有更高的复发概率(P值均<0.05)。Cox回归分析结果显示术前DCP≥200 mAU/ml(P=0.017)是肝移植术后复发的独立危险因素,另一个独立危险因素是累计肿瘤直径>9 cm(P=0.014)。χ^2检验结果显示术前血清DCP水平与性别、血清γ-谷氨酰转移酶水平、血清甲胎蛋白水平、累计肿瘤直径、血管侵犯、肿瘤分化以及肝癌肝移植标准相关(P值均<0.05)。结论术前血清DCP预测肝癌肝移植术后复发,可以作为现有肝癌肝移植标准的补充,进一步更加精确地筛选出术后复发风险小和预后好的肝细胞癌患者来接受移植手术,进一步改善肝癌肝移植的疗效。

Objective To explore the clinical value of serum des-γ-carboxy prothrombin(DCP)in predicting hepatocellular carcinoma recurrence after liver transplantation.Methods A total of 115 cases with hepatocellular carcinoma who underwent liver transplantation in Zhongshan Hospital Affiliated to Fudan University from October 2016 to December 2018 were retrospectively analyzed.Receiver operating characteristic curve analysis,Mann-Whitney U test,Kaplan-Meier method,Log-Rank test,χ^2 test,univariate and multivariate Cox regression analysis and other statistical methods were used to explore the value of DCP in predicting tumor recurrence after liver transplantation and its correlation with clinicopathological characteristics.Results The preoperative serum DCP level in recurrent population after liver transplantation was significantly higher than that in non-recurrent population(P<0.001).The optimal cut-off value of preoperative DCP for predicting recurrence was 200mAU/ml with the use of receiver operating characteristic curve.The sensitivity,specificity,Youden’s index and the receiver operating characteristic curve was 87.90%,57.30%,0.452,and 0.726,respectively.Survival analysis results grouped by this cut-off value showed that patients with preoperative DCP≥200mAU/ml had a higher probability of recurrence(P<0.001).Further,subgroup survival analysis showed that patients with preoperative DCP≥200 mAU/ml had a higher probability of recurrence than other cases of alpha-fetoprotein negative subgroup,cumulative tumor diameter≤9 cm subgroup and Milan criteria subgroup(P<0.05).Cox regression analysis showed that preoperative DCP≥200 mAU/ml(P=0.017)and cumulative tumor diameter>9 cm(P=0.014)was an independent risk factor for recurrence after liver transplantation.χ^2 test results showed that preoperative serum DCP level was correlated with gender,serum gamma glutamyltransferase level,serum alpha fetoprotein level,cumulative tumor diameter,vascular invasion,tumor differentiation and liver cancer transplant criteria(P<0.05).Conclusion Preoperative serum DCP can be used as a supplement to the existing liver cancer transplant criteria to predict hepatocellular carcinoma recurrence after liver transplantation.In addition,the accurate screening of patients with low risk of HCC recurrence after liver transplantation can improve the prognosis and efficacy of liver transplant patients.