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中华临床医师杂志(电子版) ›› 2018, Vol. 12 ›› Issue (05) : 268 -272. doi: 10.3877/cma.j.issn.1674-0785.2018.05.003

所属专题: 文献

临床研究

HBV基因型、基因亚型及基因变异与原发性肝癌的关系
石光英1, 郭新文2, 谢敬东3,()   
  1. 1. 830002 乌鲁木齐,新疆生产建设兵团医院消化肝病科
    2. 843000 新疆维吾尔自治区阿克苏地区第一人民医院消化科
    3. 200025 上海交通大学医学院附属瑞金医院感染科
  • 收稿日期:2017-12-29 出版日期:2018-03-01
  • 通信作者: 谢敬东
  • 基金资助:
    新疆兵团科技计划项目(2013AB028)院级课题(2016AD011)

Correlation of hepatocellular carcinoma with hepatitis B virus genotype, subgenotype, and mutation

Guangying Shi1, Xinwen Guo2, Jingdong Xie3,()   

  1. 1. Department of Hepatology, Xinjiang Production and Construction Corps Hospital, Urumqi 830002, China
    2. Department of Digestive Medicine, Aksu Region First People's Hospital of Xinjiang Uygur Autonomous Region, Aksu 843000, China
    3. Department of Infection, Ruijin Hospital, Shanghai Jiaotong University Medical College, Shanghai 200025, China
  • Received:2017-12-29 Published:2018-03-01
  • Corresponding author: Jingdong Xie
  • About author:
    Corresponding author: Xie Jingdong, Email:
引用本文:

石光英, 郭新文, 谢敬东. HBV基因型、基因亚型及基因变异与原发性肝癌的关系[J]. 中华临床医师杂志(电子版), 2018, 12(05): 268-272.

Guangying Shi, Xinwen Guo, Jingdong Xie. Correlation of hepatocellular carcinoma with hepatitis B virus genotype, subgenotype, and mutation[J]. Chinese Journal of Clinicians(Electronic Edition), 2018, 12(05): 268-272.

目的

探讨乙型肝炎病毒(HBV)不同基因型、基因亚型及基因变异与原发性肝癌(PHC)的关系,为制定PHC的预防和治疗措施提供科学依据。

方法

收集新疆生产建设兵团医院2013年3月至2016年3月共4例感染HBV基础上的PHC患者,利用荧光定量PCR法检测HBV DNA,酶联免疫法检测HBeAg。应用PCR方法检测患者HBV基因型、基因亚型分布特征,检测HBV基因变异情况。

结果

此4例感染HBV基础上的PHC患者中,3例患者HBeAg(+),HBeAg阳性率为75%。4例患者中3例HBV DNA(+),定量检测结果分别为2.03×105 IU/ml、2.56×106 IU/ml、3.12×105 IU/ml;1例患者HBV DNA(-)。检测患者基因型为B型1例(B2亚型),C型3例(C1亚型1例,C2亚型2例)。HBV B2亚型、C1亚型和1例C2亚型患者,分别在APC、CTNNB1、IGF2R基因处出现基因变异;1例C2亚型患者(80岁),在UGT1A5、ZFYVE16、MALRD1基因的外显子序列检测中发现移码变异。

结论

HBV基因型,尤其是C型可能是PHC发生的危险因素。基因变异与PHC的发生发展可能也存在密切关系。

Objective

To analyze the correlation of hepatocellular carcinoma with hepatitis B virus genotype, subgenotype, or mutation, so as to provide a scientific basis for the prevention of hepatocellular carcinoma.

Methods

Totally four patients with HBV associated primary hepatocellular carcinoma (PHC) were collected in this study. HBV DNA was tested by qRT-PCR. HBeAg was tested by enzyme linked immunosorbent assay. HBV genotypes were determined by PCR-restriction fragment length polymorphism. HBV subgenotypes were determined by nested PCR. HBV DNA mutations were determined by PCR or direct sequencing.

Results

Among the four patients with PHC, the positive rate of HBeAg was 75%. HBV DNA quantitative detection was positive in three patients (2.03×105 IU/mL, 2.56×106 IU/mL, and 3.12×105 IU/mL), and one case was HBV DNA negative. The detected genotypes included type B in one case (subtype B2) and type C in three cases, among which one was subtype C1 and two were subtype C2. Thus, in PHC patients, the main genotype and subgenotype were C and C2, respectively.

Conclusion

HBV genotypes, especially genotype C and subgenotype C2 variants, may be risk factors for the development of PHC. The gene mutations of HBV DNA may be closely related to the occurrence and development of PHC.

表1 3例原发性肝癌患者基因变异情况
表2 1例80岁原发性肝癌患者(乙型肝炎病毒C2亚型)基因变异情况
1
黄元亮. 乙型肝炎病毒感染与原发性肝癌的相关性临床研究[J].中华医院感染学杂志, 2013, 23(22):5407-5409.
2
Alexopoulou A, Karayiannis P. HBeAg negative variants and their role in the natural history of chronic hepatitis B virus infection [J].World J Gastroenterol, 2014, 20(24):7644-7652.
3
王慧. HBV基因变异在HBV相关原发性肝细胞癌中的临床意义研究[D]. 上海: 第二军医大学, 2015.
4
周国平,白敬羽,罗立波, 等. 肝癌患者血清中乙型肝炎病毒前C和BCP区基因变异的临床研究[J].临床检验杂志, 2006, 24(5):344-345.
5
李春青,荀运浩,梁娴, 等. HBV BCP区1762/1764位点变异对肝脏疾病进展及预后的影响[J].中西医结合肝病杂志, 2016, 26(4):207-209.
6
李朝霞,杨建军,毛维武, 等. 乙型肝炎病毒基因变异与原发性肝癌的关系[J]. 医学综述, 2012, 18(20):3382-3384.
7
Vratnica Z, Zehender G, Ebranati E, et al. Hepatitis B virus genotype and subgenotype prevalence and distribution in Montenegro [J]. J Med Virol, 2015, 87(5):807-813.
8
王贵强,王福生,成军, 等. 慢性乙型肝炎防治指南(2015年版) [J/CD].中华实验和临床感染病杂志(电子版), 2015, 9(5):570-589.
9
张勇扬,王爱平,潘金顺, 等. 乙肝病毒基因型及基因变异与原发性肝癌的相关性[J]. 江苏医药, 2011, 37(11):1279-1281.
10
张正国,贺庆伟,张晋军. 原发性肝癌患者HBV DNA水平和基因分型及HBV-M检测的相关性分析[J].中国卫生检验杂志, 2013, 23(11):2501-2503.
11
李朝霞,张文杰,杨建军, 等. 甘肃地区乙型肝炎病毒基因型和基因变异与原发性肝癌的关系[J]. 国际流行病学传染病学杂志, 2013, 40(2):89-93.
12
谢佳新,张海谱,高秋菊, 等. 石家庄地区乙肝病毒基因型分布及其与疾病进展关联研究[J]. 现代预防医学, 2017, 44(7):1161-1165.
13
Kramvis A, Paraskevis D. Subgenotype A1 of HBV-tracing human migrations in and out of Africa [J]. Antivir Ther, 2013, 18(3 Pt B):513-521.
14
Jemal A, Bray F, Center MM, et al. Global cancer statistics [J]. CA Cancer J Clin, 2011, 61(2):69-90.
15
Fujimori M, Tokino T, Hino O, et al. Allelotype study of primary hepatocellular carcinoma [J]. Cancer Res, 1991, 51(1):89-93.
16
Nagai H, Pineau P, Tiollais P, et al.Comprehensive allelotyping of human hepatocellular carcinoma [J]. Oncogene, 1997, 14(24):2927-2933.
17
Yeh SH, Chen PJ, Chen HL, et al. Frequent genetic alterations at the distal region of chromosome 1p in human hepatocellular carcinomas [J]. Cancer Res, 1994, 54(15):4188-4192.
18
Chen CJ, Yang HI, Su J, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level [J]. JAMA, 2006, 295(1):65-73.
19
Carman WF, Jacyna MR, Hadziyannis S, et al.Mutation preventing formation of hepatitis B e antigen in the patients with chronic hepatitis B infection [J]. Lancet, 1989, 2(8663):588-591.
20
吴龙,钱叶本,朱立新, 等. 肝细胞癌中SFRP1和APC基因启动子甲基化与其mRNA的表达[J].中国普通外科杂志, 2008, 17(1):29-33.
21
Kiran M, Chawla YK, Kaur J. Methylation profiling of tumor suppressor genes and oncogenes in hepatitis virus-related hepatocellular carcinoma in northern India [J]. Cancer Genet Cytogenet, 2009, 195(2):112-119.
22
Li M, Zhao H, Zhang X, et al. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma [J]. Nat Genet, 2011, 43(9):828-829.
23
Ding SL, Yang ZW, Wang J, et al. Integrative analysis of aberrant Wnt signaling in hepatitis B virus-related hepatocellular carcinoma [J].World J Gastroenterol, 2015, 21(20):6317-6328.
24
Johnson AD, Kavousi M, Smith AV, et al. Genome-wide association meta-analysis for total serum bilirubin levels [J].Hum Mol Genet, 2009, 18(14):2700-2710.
25
Zuo X, Sun L, Yin X, et al.Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis [J]. Nat Commun, 2015, 6:6793.
26
Zubenko GS, Hughes HB 3rd, Stiffler JS. D10S1423 identifies a susceptibility locus for Alzheimer′s disease in a prospective, longitudinal, double-blind study of asymptomatic individuals [J]. Mol Psychiatry, 2001, 6(4):413-419.
27
李明. FLG基因功能缺失突变及其疾病相关性研究[D]. 上海: 上海交通大学, 2012.
28
Chen L, Su L, Li J, et al.Hypermethylated FAM5C and MYLK in serum as diagnosis and pre-warning markers for gastric cancer [J]. Dis Markers, 2012, 32(3):195-202.
29
Lee WS, Seo G, Shin HJ, et al.Identification of differentially expressed genes in microsatellite stable HNPCC and sporadic colon cancer [J]. J Surg Res, 2008, 144(1):29-35.
30
谭翔,陈铭伍,王永勇, 等. 肌球蛋白轻链激酶和肌球蛋白轻链9基因在非小细胞肺癌中的表达及意义[J]. 广西医学, 2014, 36(10):1371-1373.
31
吴伟刚,刘妙娜,刘利平, 等. CENPK基因过表达载体的构建及鉴定[J].中国肿瘤, 2015, 24(6):505-509.
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