Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, P.R. China.
Department of Pathology, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, P.R. China.
Anticancer Res. 2020 Jan;40(1):245-252. doi: 10.21873/anticanres.13946.
It has been shown that the integration of hepatitis B virus (HBV) gene into the host genome is a high-risk factor for development of hepatocellular carcinoma (HCC). However, the relationship between HBV S-integrated human extra spindle pole bodies-like 1 (ESPL1) gene and HCC is unknown. This study was designed to detect HBV S-integrated human ESPL1 fusion gene in patients with HCC for potentially using this fusion gene as a biomarker for HCC diagnosis.
Nineteen and 70 patients with chronic hepatitis B (CHB) were recruited to the experimental and control groups, respectively, and both groups underwent an effective nucleoside/nucleotide analog therapy and follow-up for HCC occurrence for up to 11 years. HCC tissues were obtained by surgical resection from the experimental group, while liver tissues were collected by liver biopsy in the control group prior to treatment with nucleoside/nucleotide analogs. Alu polymerase chain reaction was used to assess HBV S gene integration in the liver tissues from both groups. HBV S-integrated human ESPL1 fusion gene was then detected in patients with HBV S gene integration using a gene database.
All patients in the experimental group developed HCC, whereas no HCC was diagnosed in the control group. HBV S gene integration was identified in 12 out of 19 HCC tissues in the experimental group, giving a detection rate of 63.2%, which was significantly greater than that of 15.7% (11/70) in the control group (p<0.001). We further showed that HBV S-integrated human ESPL1 fusion gene was detected in eight patients (rate of 66.7%) among the 12 patients with HCC with HBV S gene integration in the experimental group, whereas the fusion gene was not detectable in any of the patients in the control group (p=0.001).
This research demonstrates a high detection rate of HBV S-integrated human ESPL1 fusion gene in patients with HBV-related HCC and shows that this fusion gene appears to be associated with HCC development in patients with CHB. These findings suggest that HBV S-integrated human ESPL1 fusion gene may potentially serve as a biomarker for early detection of HCC in HBV-infected populations.
已有研究表明，乙型肝炎病毒（HBV）基因整合到宿主基因组是肝细胞癌（HCC）发生的高危因素。然而，HBV S 整合人额外纺锤极体样 1（ESPL1）基因与 HCC 的关系尚不清楚。本研究旨在检测 HCC 患者中 HBV S 整合人 ESPL1 融合基因，以期将该融合基因作为 HCC 诊断的生物标志物。
19 例慢性乙型肝炎（CHB）患者纳入实验组，70 例患者纳入对照组，两组均接受有效的核苷（酸）类似物治疗，并随访 HCC 发生情况，最长达 11 年。实验组通过手术切除获得 HCC 组织，对照组在接受核苷（酸）类似物治疗前通过肝活检获得肝组织。采用 Alu 聚合酶链反应检测两组肝组织中 HBV S 基因整合。然后，使用基因数据库检测 HBV S 基因整合患者中的 HBV S 整合人 ESPL1 融合基因。
实验组所有患者均发展为 HCC，而对照组无一例 HCC 诊断。实验组 19 例 HCC 组织中有 12 例检测到 HBV S 基因整合，检出率为 63.2%，明显高于对照组的 15.7%（11/70）（p<0.001）。我们进一步发现，在实验组中 12 例 HBV S 基因整合的 HCC 患者中，有 8 例（66.7%）检测到 HBV S 整合人 ESPL1 融合基因，而对照组中无患者检测到融合基因（p=0.001）。
本研究表明，HBV 相关 HCC 患者中 HBV S 整合人 ESPL1 融合基因的检出率较高，且该融合基因似乎与 CHB 患者 HCC 的发生有关。这些发现提示 HBV S 整合人 ESPL1 融合基因可能作为 HBV 感染人群 HCC 早期检测的潜在生物标志物。
