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A novel HBx genotype serves as a preoperative predictor and fails to activate the JAK1/STATs pathway in hepatocellular carcinoma.
Xu, Qing-Guo; Yuan, Sheng-Xian; Tao, Qi-Fei; Yu, Jian; Cai, Jie; Yang, Yuan; Guo, Xing-Gang; Lin, Kong-Ying; Ma, Jin-Zhao; Dai, De-Shu; Wang, Zhen-Guang; Gu, Fang-Ming; Zhao, Ling-Hao; Li, Le-Qun; Liu, Jing-Feng; Sun, Shu-Han; Zang, Yun-Jin; Liu, Hui; Yang, Fu; Zhou, Wei-Ping.
Affiliation
  • Xu QG; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China; Organ Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, China.
  • Yuan SX; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Tao QF; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Yu J; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Cai J; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Yang Y; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Guo XG; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Lin KY; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China; Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian, China.
  • Ma JZ; The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
  • Dai DS; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Wang ZG; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Gu FM; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Zhao LH; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • Li LQ; Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Guangxi, China.
  • Liu JF; Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian, China.
  • Sun SH; The Department of Medical Genetics, Second Military Medical University, Shanghai, China.
  • Zang YJ; Organ Transplantation Center, Affiliated Hospital of Qingdao University, Qingdao, China.
  • Liu H; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China. Electronic address: liuhuigg@hotmail.com.
  • Yang F; The Department of Medical Genetics, Second Military Medical University, Shanghai, China. Electronic address: yangfusq1997@smmu.edu.cn.
  • Zhou WP; The Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China; Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer (SMMU), Ministry of Education, Shanghai, China; Shanghai Key Laboratory of Hepatobiliary Tumor Biology (EHBH), Shang
J Hepatol ; 70(5): 904-917, 2019 05.
Article in En | MEDLINE | ID: mdl-30654066
ABSTRACT
BACKGROUND &

AIMS:

Genetic variability in the hepatitis B virus X gene (HBx) is frequently observed and is associated with hepatocellular carcinoma (HCC) progression. However, a genotype classification based on the full-length HBx sequence and the impact of genotypes on hepatitis B virus (HBV)-related HCC prognosis remain unclear. We therefore aimed to perform this genotype classification and assess its clinical impact.

METHODS:

We classified the genotypes of the full-length HBx gene through sequencing and a cluster analysis of HBx DNA from a cohort of patients with HBV-related HCC, which served as the primary cohort (n = 284). Two independent HBV-related HCC cohorts, a validation cohort (n = 171) and a serum cohort (n = 168), were used to verify the results. Protein microarray assay analysis was performed to explore the underlying mechanism.

RESULTS:

In the primary cohort, the HBx DNA was classified into 3 genotypes HBx-EHBH1, HBx-EHBH2, and HBx-EHBH3. HBx-EHBH2 (HBx-E2) indicated better recurrence-free survival and overall survival for patients with HCC. HBx-E2 was significantly correlated with the absence of liver cirrhosis, a small tumor size, a solitary tumor, complete encapsulation and Barcelona Clinic Liver Cancer (BCLC) stage A-0 tumors. Additionally, HBx-E2 served as a significant prognostic factor for patients with BCLC stage B HCC after hepatectomy. Mechanistically, HBx-E2 is unable to promote proliferation in HCC cells and normal hepatocytes. It also fails to activate the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3)/STAT5 pathway.

CONCLUSION:

Our study identifies a novel HBx genotype that is unable to promote the proliferation of HCC cells and suggests a potential marker to preoperatively predict the prognosis of patients with BCLC stage B, HBV-associated, HCC. LAY

SUMMARY:

We classified a novel genotype of the full-length hepatitis B virus X gene (HBx), HBx-E2. This genotype was identified in tumor and nontumor tissues from patients with hepatitis B virus-related hepatocellular carcinoma. HBx-E2 could preoperatively predict the prognosis of patients with intermediate stage hepatocellular carcinoma, after resection.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trans-Activators / Carcinoma, Hepatocellular / STAT Transcription Factors / Janus Kinase 1 / Viral Regulatory and Accessory Proteins / Liver Neoplasms Type of study: Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: J Hepatol Journal subject: GASTROENTEROLOGIA Year: 2019 Type: Article Affiliation country: China
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trans-Activators / Carcinoma, Hepatocellular / STAT Transcription Factors / Janus Kinase 1 / Viral Regulatory and Accessory Proteins / Liver Neoplasms Type of study: Prognostic_studies / Risk_factors_studies Limits: Humans Language: En Journal: J Hepatol Journal subject: GASTROENTEROLOGIA Year: 2019 Type: Article Affiliation country: China