HBV相关肝细胞癌组织中HBV cccDNA和HBsAg降低。

StephenW

Med Oncol. 2018 Aug 16;35(10):127. doi: 10.1007/s12032-018-1191-7.
Reduced HBV cccDNA and HBsAg in HBV-associated hepatocellular carcinoma tissues.
Tantiwetrueangdet A1, Panvichian R2, Sornmayura P3, Sueangoen N1, Leelaudomlipi S4.
Author information

1
    Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
2
    Division of Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama 6 Road, Rajthevi, Bangkok, 10400, Thailand. [email protected].
3
    Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
4
    Department of Surgery, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Abstract

Approximately 50% of hepatocellular carcinoma (HCC) is attributable to chronic infection with hepatitis B virus (HBV). Serum hepatitis B surface antigen (HBsAg) is an important diagnostic marker of HBV infection, whereas intrahepatic HBV covalently closed circular DNA (cccDNA) is a surrogate marker of HBV persistence. This study aimed to investigate relationships between serum HBsAg, intrahepatic HBsAg, and intrahepatic cccDNA in HBV-associated HCC. Intrahepatic HBsAg was determined by immunohistochemistry in matched non-cancerous and HCC tissues from 88 patients; 56 patients (63.64%) were serum HBsAg positive. In serum HBsAg-positive group, intrahepatic HBsAg was positive staining in 73.2% of non-cancerous tissues, but only in 10.7% of HCC tissues. Significant correlation between serum HBsAg and intrahepatic HBsAg was observed in non-cancerous tissues (p < 0.001), but not in HCC tissues (p = 0.415). Absolute quantification of intrahepatic cccDNA was performed by droplet digital PCR in tissues from 30 patients; 18 patients (60%) were serum HBsAg positive. In serum HBsAg-positive group, intrahepatic cccDNA was detected in 66.66% of non-cancerous tissues, but only in 5.55% of HCC tissue; intrahepatic cccDNA levels in non-cancerous tissues were significantly higher than those in HCC tissues (p < 0.001), and correlated with serum HBsAg (p < 0.01). Significant correlations between intrahepatic HBsAg and intrahepatic cccDNA were found in both non-cancerous tissues (p < 0.01) and HCC tissues (p < 0.05). We concluded that HBV cccDNA and intrahepatic HBsAg in HBV-associated HCC tissues were significantly reduced, as compared with matched non-cancerous tissues. This warrants further investigation into the impacts and the cause(s) of cccDNA reduction in HBV-associated HCC tissues, which might yield novel immune-related therapy for HBV-associated HCC.
KEYWORDS:

HBV; HBsAg; HCC; cccDNA; ddPCR

PMID:
    30116916
DOI:
    10.1007/s12032-018-1191-7

StephenW

Med Oncol。 2018年8月16日; 35（10）：127。 doi：10.1007 / s12032-018-1191-7。
HBV相关肝细胞癌组织中HBV cccDNA和HBsAg降低。
Tantiwetrueangdet A1，Panvichian R2，Sornmayura P3，Sueangoen N1，Leelaudomlipi S4。
作者信息

1
    泰国曼谷玛希隆大学Ramathibodi医院医学院研究中心。
2
    医学肿瘤学系，医学院，医学院，Ramaidibodi医院，Mahidol大学，Rama 6路，Rajthevi，曼谷，10400，泰国。 [email protected]。
3
    泰国曼谷玛希隆大学Ramathibodi医院医学院病理学系。
4
    泰国曼谷玛希隆大学Ramathibodi医院医学系外科。

抽象

大约50％的肝细胞癌（HCC）可归因于乙型肝炎病毒（HBV）的慢性感染。血清乙型肝炎表面抗原（HBsAg）是HBV感染的重要诊断标志物，而肝内HBV共价闭合环状DNA（cccDNA）是HBV持续性的替代指标。本研究旨在探讨HBV相关性HCC患者血清HBsAg，肝内HBsAg和肝内cccDNA之间的关系。通过免疫组织化学法检测88例患者的非癌和肝癌组织中的肝内HBsAg; 56例患者（63.64％）血清HBsAg阳性。在血清HBsAg阳性组中，肝内HBsAg阳性染色在73.2％的非癌组织中，但仅在10.7％的HCC组织中阳性染色。在非癌组织中观察到血清HBsAg与肝内HBsAg之间的显着相关性（p <0.001），但在HCC组织中未观察到（p = 0.415）。通过液滴数字PCR在30名患者的组织中进行肝内cccDNA的绝对定量; 18名患者（60％）血清HBsAg阳性。在血清HBsAg阳性组中，66.66％的非癌组织中检测到肝内cccDNA，但仅在5.55％的HCC组织中检测到;非癌组织中的肝内cccDNA水平显着高于HCC组织（p <0.001），并与血清HBsAg相关（p <0.01）。在非癌组织（p <0.01）和HCC组织（p <0.05）中发现了肝内HBsAg和肝内cccDNA之间的显着相关性。我们得出结论，与匹配的非癌组织相比，HBV相关的HCC组织中的HBV cccDNA和肝内HBsAg显着降低。这需要进一步调查HBV相关HCC组织中cccDNA减少的影响和原因，这可能会产生针对HBV相关HCC的新型免疫相关疗法。
关键词：

HBV;乙肝表面抗原; HCC; cccDNA的; ddPCR

结论：
    30116916
DOI：
    10.1007 / s12032-018-1191-7