原发性肝细胞癌患者血清HBcrAg与组织中HBV DNA载量的关系

doi:10.3969/j.issn.1673-8640.2016.011.005

摘要/Abstract

摘要：

目的分析一种新型的乙型肝炎病毒（HBV）感染标志物——乙型肝炎核心相关抗原（HBcrAg）与原发性肝细胞癌（HCC）患者癌组织和癌旁组织内共价闭合环状DNA（cccDNA）、HBV DNA水平的关系。方法收集行肝癌切除术的HBV感染相关的HCC患者95例,用化学发光法检测患者血清HBcrAg水平,同时用聚合酶链反应（PCR）荧光探针法分别对配对的癌组织和癌旁组织内cccDNA、HBV DNA进行定量检测。结果乙型肝炎e抗原（HBeAg）⁺/乙型肝炎e抗体（HBeAb）^-组、HBeAg⁺/HBeAb⁺组、HBeAg^-/HBeAb⁺组HBcrAg水平分别为（6.41±1.18）、（5.80±0.50）和（5.16±0.94）lgU/mL,3个组间差异有统计学意义（P<0.001）。HCC患者HBcrAg与癌旁组织cccDNA和癌旁组织HBV DNA具有相关性（r=0.359、0.440,P<0.001）,TNMⅠ期 HCC患者HBcrAg与癌旁组织cccDNA和癌旁组织HBV DNA具有相关性（r=0.491、0.578,P<0.01）,TNMⅡ期HCC患者HBcrAg与癌旁组织cccDNA和癌旁组织HBV DNA具有相关性（r=0.339、0.402,P<0.05）,TNMⅢ期HCC患者HBcrAg与癌旁组织cccDNA和癌旁组织HBV DNA无相关性。结论 HBcrAg可以辅助区分发生HBeAg血清学转换和未发生转换的患者;在乙型肝炎表面抗原（HBsAg）⁺HCC患者中,HBcrAg与癌旁组织HBV DNA及癌旁组织cccDNA具有一定的相关性,但其相关性未表现出比现有血清标志物（HBeAg及HBV DNA）更好。

Abstract:

Objective To assess the correlations of a newly-developed hepatitis B virus（HBV） infection marker,hepatitis B core-related antigen（HBcrAg）,with covalent closed circular DNA（cccDNA） and HBV DNA in tumor tissue and adjacent non-tumor tissue among hepatocellular carcinoma（HCC） patients. Methods A total of 95 HBV infection-related patients who received hepatic resection for HCC were enrolled. Serum HBcrAg were determined by chemiluminescence immunoassay. HBV DNA and cccDNA in tumor tissue and adjacent non-tumor tissue were quantified by polymerase chain reaction（PCR） fluorescent probe. Results The levels of HBcrAg in hepatitis B e antigen（HBeAg）⁺/hepatitis B e antibody（HBeAb）^- group,HBeAg⁺/HBeAb⁺ group and HBeAg^-/HBeAb⁺ group were （6.41±1.18）,（5.80±0.50） and（5.16±0.94）lgU/mL,respectively,and there was statistical significance among these 3 groups（P<0.001）. There were correlations of HBcrAg with adjacent non-tumor tissue cccDNA and adjacent non-tumor tissue HBV DNA in HCC patients（r=0.359 and 0.440,P<0.001）. In HCC patients of TNM stage Ⅰ,HBcrAg was associated with adjacent non-tumor tissue cccDNA and adjacent non-tumor tissue HBV DNA（r=0.491 and 0.578,P<0.01）. In HCC patients with TNM stage Ⅱ,HBcrAg was correlated with adjacent non-tumor tissue cccDNA and adjacent non-tumor tissue HBV DNA（r=0.339 and 0.402,P<0.05）. However, in HCC patients with TNM stage Ⅲ,no correlation of HBcrAg and adjacent non-tumor tissue cccDNA and adjacent non-tumor tissue HBV DNA. Conclusions HBcrAg can help with distinguishing HBeAg positive and negative HCC patients. Although HBcrAg has correlations with adjacent non-tumor tissue HBV DNA and cccDNA in hepatitis B surface antigen（HBsAg）⁺ HCC patients,it does not show better correlations than other serum markers such as HBeAg and HBV DNA.

Key words: Hepatitis B core-related antigen, Hepatitis B e antigen, DNA, Hepatitis B virus, Hepatocellular carcinoma

中图分类号:

R446.62

李慧明, 贾健安, 王蒙蒙, 顾星, 房萌, 高春芳. 原发性肝细胞癌患者血清HBcrAg与组织中HBV DNA载量的关系[J]. 检验医学, 2016, 31(11): 948-952.

LI Huiming, JIA Jian'an, WANG Mengmeng, GU Xing, FANG Meng, GAO Chunfang. Correlation between serum HBcrAg and intracellular HBV DNA in patients with hepatocellular carcinoma[J]. Laboratory Medicine, 2016, 31(11): 948-952.

图/表 3

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组别	HBcrAg与各指标的r值（P值）
组别	血清HBV DNA	癌组织cccDNA	癌组织HBV DNA	癌旁组织cccDNA	癌旁组织HBV DNA
HBeAg⁺/HBeAb^-组	0.151（0.538）	-0.068（0.783）	-0.161（0.511）	0.225（0.355）	0.327（0.131）
HBeAg⁺/HBeAb⁺组	0.228（0.379）	0.456（0.066）	0.211（0.046）	0.168（0.518）	0.215（0.407）
HBeAg^-/HBeAb⁺组	0.541（<0.001）	0.145（0.305）	0.032（0.812）	0.341（0.008）	0.377（0.003）
合计	0.486（<0.001）	0.129（0.230）	0.047（0.651）	0.359（<0.001）	0.440（<0.001）

组别	HBcrAg与各指标的r值（P值）
组别	血清HBV DNA	癌组织cccDNA	癌组织HBV DNA	癌旁组织cccDNA	癌旁组织HBV DNA
HBeAg⁺/HBeAb^-组	0.151（0.538）	-0.068（0.783）	-0.161（0.511）	0.225（0.355）	0.327（0.131）
HBeAg⁺/HBeAb⁺组	0.228（0.379）	0.456（0.066）	0.211（0.046）	0.168（0.518）	0.215（0.407）
HBeAg^-/HBeAb⁺组	0.541（<0.001）	0.145（0.305）	0.032（0.812）	0.341（0.008）	0.377（0.003）
合计	0.486（<0.001）	0.129（0.230）	0.047（0.651）	0.359（<0.001）	0.440（<0.001）

TNM分期	癌旁组织cccDNA与各指标的r值			癌旁组织HBV DNA与各指标的r值
TNM分期	HBcrAg	血清HBV DNA	HBeAg	HBcrAg	血清HBV DNA	HBeAg
Ⅰ期	0.491^**	0.590^**	0.515^**	0.578^**	0.714^**	0.459^**
Ⅱ期	0.339^*	0.360	0.705^**	0.402^*	0.421^*	0.554^**
Ⅲ期	0.192	0.703^**	0.415^*	0.302	0.807^**	0.403^*

TNM分期	癌旁组织cccDNA与各指标的r值			癌旁组织HBV DNA与各指标的r值
TNM分期	HBcrAg	血清HBV DNA	HBeAg	HBcrAg	血清HBV DNA	HBeAg
Ⅰ期	0.491^**	0.590^**	0.515^**	0.578^**	0.714^**	0.459^**
Ⅱ期	0.339^*	0.360	0.705^**	0.402^*	0.421^*	0.554^**
Ⅲ期	0.192	0.703^**	0.415^*	0.302	0.807^**	0.403^*

指标	癌旁组织cccDNA			癌旁组织HBV DNA
指标	标准化系数	r²值	P值	标准化系数	r²值	P值
年龄	0.261	0.414	0.002	0.046	0.484	0.574
血清HBV DNA	0.419		<0.001	0.566		<0.001
HBeAg	0.281		0.002	0.217		0.008
白蛋白	-0.089		0.296	-0.168		0.031
HBcrAg	-0.019		0.855	0.041		0.673