血清HBX准种及其在肝细胞癌中的整合之间的关联

StephenW

Int J Clin Exp Pathol. 2017 Dec 1;10(12):11857-11866. eCollection 2017.
Associations between serum HBX quasispecies and their integration in hepatocellular carcinoma.
Fang X1, Wu HH1, Ren JJ1, Liu HZ1, Li KZ1, Li JL1, Tang YP1, Xiao CC1, Huang TR1, Deng W1.
Author information

1
    Department of Experimental Research, Affiliated Tumor Hospital of Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.

Abstract

HBV quasispecies are closely related to the course and outcome of liver disease. However, whether the complexity and diversity of HBX quasispecies affects its integration in the liver cell and thereby enhances the resultant carcinogenesis is still not clear. 15 HCC patients were recruited; genomic DNA and HBV DNA were extracted from liver cancer tissue and serum respectively. The integrated HBX fragment in liver cancer tissue was amplified by Alu repeat sequence-polymerase chain reaction (Alu-PCR) and sequenced. The serum HBX gene was amplified by nested PCR and sequenced. Quasispecies complexity and diversity, phylogenetic characteristics, lymphocyte count and survival time between HBX-integrated and HBX-unintegrated patients were evaluated. Results showed that the integrated HBX fragment was detected in the tumor tissue of nine patients, and the integration rate was 60.00% (9/15). Compared with the HBX-unintegrated patients, the HBX-integrated patients had a higher quasispecies complexity (P=0.028 and 0.004, at the nucleotide and amino acid levels, respectively). The HBX-integrated patients had a tendency of higher quasispecies diversity, lower lymphocyte count and the survival time. A total of 12 mutation sites were revealed in the HBX-integrated fragment after alignment with the reference sequence. In these, the HBX-integrated groups had significantly higher mutation frequencies at C1497T, A1630G, G1721A, A1762T/G1764A and A1774G. This study revealed influence factors of HBX integration both in virus and the host. The increased complexity and diversity of HBX quasispecies might destroy the host immune balance, and lead to HBX integration ultimately.

IJCEP Copyright © 2017.
KEYWORDS:

Hepatitis B virus X gene; hepatocellular carcinoma; integration; quasispecies

PMID:
    31966550

StephenW

Int J临床Exp Pathol。 2017年12月1日; 10（12）：11857-11866。 eCollection 2017。
血清HBX准种及其在肝细胞癌中的整合之间的关联。
房X1，吴HH1，任JJ1，刘HZ1，李KZ1，李JL1，唐YP1，肖CC1，黄TR1，邓W1。
作者信息

1个
    广西医科大学附属肿瘤医院实验研究室，广西壮族自治区南宁530021

抽象

HBV准种与肝病的病程和结局密切相关。然而，尚不清楚HBX准种的复杂性和多样性是否会影响其在肝细胞中的整合并从而增强其致癌作用。招募了15例HCC患者；从肝癌组织和血清中分别提取基因组DNA和HBV DNA。通过Alu重复序列-聚合酶链反应（Alu-PCR）扩增肝癌组织中整合的HBX片段并测序。通过巢式PCR扩增血清HBX基因并测序。评估了HBX整合患者和HBX非整合患者之间的准物种复杂性和多样性，系统发育特征，淋巴细胞计数和生存时间。结果表明，在9例患者的肿瘤组织中检测到整合的HBX片段，整合率为60.00％（9/15）。与未结合HBX的患者相比，结合HBX的患者具有更高的准物种复杂性（在核苷酸和氨基酸水平上分别为P = 0.028和0.004）。 HBX整合型患者具有较高的准种多样性，较低的淋巴细胞计数和存活时间的趋势。与参考序列比对后，在HBX整合片段中共有12个突变位点。其中，整合了HBX的组在C1497T，A1630G，G1721A，A1762T / G1764A和A1774G处具有明显更高的突变频率。这项研究揭示了HBX整合在病毒和宿主中的影响因素。 HBX准种的增加的复杂性和多样性可能破坏宿主的免疫平衡，并最终导致HBX整合。

IJCEP版权所有©2017。
关键字：

乙型肝炎病毒X基因；肝细胞癌；积分;准种

PMID：
    31966550