HBs抗原阳性和隐匿性感染的HBV相关肝细胞癌中前S / S基因的准

StephenW

Infect Agent Cancer. 2018 Feb 2;13:7. doi: 10.1186/s13027-018-0179-4. eCollection  2018.
Quasispecies variant of pre-S/S gene in HBV-related hepatocellular carcinoma with HBs antigen positive and occult infection.Hatazawa Y1, Yano Y1,2, Okada R1, Tanahashi T3, Hayashi H1, Hirano H1, Minami A1, Kawano Y1, Tanaka M4, Fukumoto T4, Murakami Y5, Yoshida M1, Hayashi Y2.
Author information
11Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017 Japan.22Division of Molecular Medicine & Medical Genetics, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan.3Department of Internal Medicine, Tokushima Prefectural Naruto Hospital, Tokushima, Japan.44Division of Hepato-Biliary-Pancreatic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.55Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Japan.

AbstractBackground: Hepatocellular carcinoma (HCC) can develop in patients who are negative for the hepatitis B surface antigen (HBsAg) in serum but positive for hepatitis B virus (HBV) DNA in the liver, referred to as occult HBV infection (OBI). Previous reports showed that HBV variants in OBI-related HCC are different from those in HBsAg-positive HCC. In the present study, HBV quasispecies based on the pre-S/S gene in OBI-related HCC patients were examined by high throughput sequencing and compared with those in HBsAg-positive HCC.
Methods: Nineteen tissue samples (9 OBI-related and 10 HBsAg-positive non-cancerous tissues) were collected at the time of surgery at Kobe University Hospital. The quasispecies with more than 1% variation in the pre-S/S region were isolated and analysed by ultra-deep sequencing.
Results: There were no significant differences in the major HBV populations, which exhibit more than 20% variation within the entire pre-S/S region, between OBI-related HCC and HBsAg-positive HCC. However, the prevalences of major populations with pre-S2 region mutations and of minor populations with polymerized human serum albumin-binding domain mutations were significantly higher in OBI-related HCC than in HBsAg-positive HCC. Moreover, the major variant populations associated with the B-cell epitope, located within the pre-S1 region, and the a determinant domain, located in the S region, were detected frequently in HBsAg-positive HCC. The minor populations of variants harbouring the W4R, L30S, Q118R/Stop, N123D and S124F/P mutations in the pre-S region and the L21F/S and L42F/S mutations in the S region were detected more frequently in OBI-related HCC than in HBsAg-positive HCC.
Conclusions: Ultra-deep sequencing revealed that the B-cell epitope domain in the pre-S1 region and alpha determinant domain in the S region were variable in HBsAg-positive HCC, although the quasispecies associated with the pre-S2 region were highly prevalent in OBI-related HCC.
Trial registration: Ref: R000034382/UMIN000030113; Retrospectively registered 25 November 2017.


KEYWORDS: HBV; HCC; Occult; Pre-S/S; Quasispecies; Ultra-deep sequencing

PMID:29434654PMCID:PMC5797373DOI:10.1186/s13027-018-0179-4

StephenW

感染代理癌症。 2018年2月2日; 13：7. Doi：10.1186 / s13027-018-0179-4。 ECollection 2018年。
HBs抗原阳性和隐匿性感染的HBV相关肝细胞癌中前S / S基因的准变异体。
Hayata H1，Minami A1，Kawano Y1，Tanaka M4，Fukumoto T4，Murakami Y5，Yoshida M1，Hayashi Y2。
作者信息

1
1日本兵库县神户市神户大学医学研究院内科系消化内科650-0017。
2
日本神户神户大学医学研究院病理学系分子医学与医学遗传学二维分析。
3
日本德岛德岛县鸣门医院内科。
4
4日本神户大学神经大学医学研究生院肝胆胰外科。
五
5日本大阪市立大学医学研究科肝脏病学系。

抽象
背景：

肝细胞癌（HCC）可发生于血清乙型肝炎表面抗原（HBsAg）阴性但肝内乙型肝炎病毒（HBV）DNA阳性的患者，称为隐匿性HBV感染（OBI）。先前的报道显示，OBI相关HCC中的HBV变体与HBsAg阳性HCC中的变体不同。在本研究中，通过高通量测序检测基于OBI相关HCC患者前S / S基因的HBV准种并与HBsAg阳性HCC相比较。
方法：

在神户大学医院手术时收集了19个组织样本（9个OBI相关和10个HBsAg阳性非癌组织）。准S / S区域变异超过1％的准种被分离并通过超深度测序进行分析。
结果：

在主要HBV群体中，在整个前S / S区域内，OBI相关HCC和HBsAg阳性HCC之间表现出超过20％的变异，没有显着差异。然而，在OBI相关的HCC中，具有pre-S2区突变的主要人群和具有聚合的人血清白蛋白结合区突变的小群体的患病率显着高于HBsAg阳性的HCC。此外，位于pre-S1内的与B细胞表位相关的主要变体群体在pre-S区域中携带W4R，L30S，Q118R / Stop，N123D和S124F / P突变的变体的少数群体和L21F S区和L42F / S突变在OBI相关的HCC中检测的频率高于HBsAg阳性的HCC。
结论：

超深度测序表明，在HBsAg阳性HCC中，前S1区的B细胞表位结构域和S区的α决定簇结构域是可变的，尽管与前S2区相关的准种在OBI-相关HCC。
试用注册：

Ref：R000034382 / UMIN000030113;回顾性注册于2017年11月25日。
关键词：

HBV; HCC;隐匿性;按;准种;超深度测序

结论：
29434654
PMCID：
PMC5797373
DOI：
10.1186 / s13027-018-0179-4

StephenW

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797373/