作者：雷秋成1,2，郑华珍3，李巧云4，邓斐文1，王巍5，李启欣3，甄作均1，陈焕伟1

单位：1.广东省佛山市第一人民医院 肝脏胰腺外科/器官移植中心，广东 佛山 528000；  2.东南大学医学院，江苏 南京 210009；  3.广东省佛山市第一人民医院 检验科，广东 佛山 528000；  4.广东省佛山市第一人民医院 临床营养中心，广东 佛山 528000；  5.广东省佛山市第一人民医院 肿瘤中心，广东 佛山 528000

Authors: Lei Qiucheng1,2, Zheng Huazhen3, Li Qiaoyun4, Deng Feiwen1, Wang Wei5, Li Qixin3, Zhen Zuojun1, Chen Huanwei1

Unit:  1.Department of Hepatopancreatic Surgery/Organ Transplantation Center, the First People’s Hospital of Foshan, Foshan 528000, Guangdong, China;   2.School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China;  3.Department of Clinical Laboratory, the First People’s Hospital of Foshan, Foshan 528000, Guangdong, China;   4.Department of Clinical Nutrition Center, the First People’s Hospital of Foshan, Foshan 528000, Guangdong, China;   5.Department of Oncology Center, the First People’s Hospital of Foshan, Foshan 528000, Guangdong, China

摘要：

目的  研究N¹,N¹²-二乙酰精胺（N¹,N¹²-diacetylspermine, DiAcSpm）水平在肝细胞癌（hepatocellular carcinoma，HCC）患者尿液中的表达和临床意义。方法  选取佛山市第一人民医院2017年8月至2018年8月住院的86例HCC患者和30例良性肝病患者，另从门诊健康体检中心选取50例健康体检者，采用免疫比浊竞争抑制法检测三组人群的尿液DiAcSpm水平。分析尿液DiAcSpm水平和HCC患者临床病理的关系，并探讨DiAcSpm对HCC患者术后复发的影响。结果  HCC患者的尿液DiAcSpm水平高于健康体检者（P<0.05），而与良性肝病患者的差异无统计学意义（P>0.05）。HCC患者尿液DiAcSpm与血清甲胎蛋白水平存在一定的正相关（r=0.75，P<0.001）。DiAcSpm诊断HCC的敏感度为0.67，特异度为0.51。根据受试者操作特征曲线cut-off 值[0.61 μmol/(g·Cre)]将HCC手术患者分为高DiAcSpm组和低DiAcSpm组，两组年龄和性别差异均无统计学意义（均P>0.05）；其中高DiAcSpm 组TNM分期和巴塞罗那分期晚于低DiAcSpm组（均P<0.05），而血管浸润在高DiAcSpm组患者中的比例高于低DiAcSpm组（P<0.05）；高DiAcSpm组HCC患者中位无瘤生存时间与低DiAcSpm组差异无统计学意义（P>0.05）。结论 DiAcSpm在HCC患者的尿液中表达升高，可能与肝癌的发生和发展密切相关, 有望成为HCC早期诊断和手术预后监测的有效指标。

关键词： 肝细胞癌；N¹,N¹²-二乙酰精胺；甲胎蛋白；肿瘤标志物

Abstract：

Objective  To investigate the expression and the significance of urinary N¹,N¹²-diacetylspermine(DiAcSpm)in the diagnosis and prognosis of hepatocellular carcinoma (HCC) patients. Method  86 HCC patients and 30 benignant liver disease patients admitted to the First People's Hospital of Foshan from August 2017 to August 2018 were selected as the study subjects, another 50 healthy persons from physical examination center of the hospital were also included. Urinary DiAcSpm level in the three groups were detected by turbidimetric inhibition immuno assay. The relationship between urinary DiAcSpm level and clinicopathological characteristics of HCC patients was analyzed. The impact of DiAcSpm on postoperative recurrence in HCC patients was analyzed. Result  The urinary DiAcSpm level of HCC patients was higher than that of healthy persons (P<0.05), but there was no statistical difference in urinary DiAcSpm level between the HCC patients and benignant liver disease patients (P>0.05) . There is a certain positive correlation between urinary DiAcSpm and serum alpha-fetoprotein levels in HCC patients (r=0.75，P<0.001). The sensitivity and specificity of DiAcSpmin diagnosing HCC was 0.67 and 0.51, respectively. Based on the cut-off value [0.61 μmol/(g·Cre)] of receiver operating characteristic curve, the HCC surgical patients were divided into high DiAcSpm group and low DiAcSpm group. There were no statistical differences in age and gender between the two groups (all P>0.05). The TNM stage and Barcelona clinic liver cancer stage in the high DiAcSpm group were later than those in the low DiAcSpm group in HCC surgical patients, respectively (all P<0.05). Venous invasion was more common in the high DiAcSpm group than in the low DiAcSpm group among HCC surgical patients (P<0.05). There was no statistical difference in the median disease free survival between the high DiAcSpm group and the low DiAcSpm group(P>0.05). Conclusion  The level of urinary DiAcSpm in HCC patients is up-regulated and maybe closely related with the occurence and progression of HCC, which is an effective biomarker for early diagnosis and surgical prognosis monitoring in HCC patients.

Key Words:  Hepatocellular carcinoma；N¹,N¹²-diacetylspermine；Alpha fetoprotein；Tumor markers