Chia-Jui Yen1, Yu-Lin Ai2, Hung-Wen Tsai3, Shih-Huang Chan4, Chia-Sheng Yen5,6,7, Kuang-Hsiung Cheng3, Yun-Ping Lee2, Chia-Wei Kao2, Yu-Chun Wang2, Yi-Lin Chen3, Cheng-Han Lin8, Tsunglin Liu8, Huey-Pin Tsai3, Jen-Ren Wang2,3,9, Ih-Jen Su10, Wenya Huang2,3,9. 1. Division of Hematology and Oncology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 2. Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 3. Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan. 4. Department of Statistics, College of Management, National Cheng Kung University, Tainan, Taiwan. 5. Department of Surgery, Chi-Mei Medical Center, Tainan, Taiwan. 6. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. 7. Department of Nursing, Meiho University, PingTung, Taiwan. 8. Department of Biotechnology and Bioindustry Sciences, College of Bioscience & Biotechnology, National Cheng Kung University, Tainan, Taiwan. 9. Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan, Taiwan. 10. Department of Biotechnology, Southern Taiwan University, Tainan, Taiwan.
Abstract
Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S2 mutant large HBV surface antigen (LHBS) is highly associated with HCC. This study analyzed the expression of the large form of surface protein in tumors and evaluated the LHBS with mutations within the pre-S2 region as a high-risk recurrence marker in HCC patients after curative hepatic resection. By analyses using immunohistochemical staining (n = 12) and western blotting (n = 22), the HBV surface protein, which is mainly comprised of the major form of HBV surface antigen, was greatly diminished in the tumors. However, LHBS was not significantly decreased in tumorous regions, suggesting that LHBS maintains its expression in cancer development. A cohort of 175 patients with HBV-related HCC who underwent curative hepatic resection was analyzed for pre-S gene mutations using Pre-S Gene Chip. Results of the multivariate regression analysis showed that the serum pre-S2 mutant level and the American Joint Committee on Cancer stage were the two main independent high-risk factors for recurrence. A Cox proportional hazards analysis also revealed a prediction model, which indicated the recurrence-free survival rate along with the time after surgery; this was developed and further validated in an independent HCC cohort. Receiver operating characteristic curve analysis revealed that the model showed close sensitivities in the main and validation cohorts (area under the curve values, 0.741 and 0.704, respectively). Conclusion: Unlike the major HBV surface antigen, LHBS is mostly expressed in the tumorous regions of HBV-induced HCC, indicating that it plays a unique role in tumor progression; the relative level of pre-S2 mutant in serum is, independently of tumor stage, an important high-risk marker for HCC recurrence after primary hepatic resection. (Hepatology 2018).
Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S2 mutant large HBV surface antigen (LHBS) is highly associated with HCC. This study analyzed the expression of the large form of surface protein in tumors and evaluated the LHBS with mutations within the pre-S2 region as a high-risk recurrence marker in HCC patients after curative hepatic resection. By analyses using immunohistochemical staining (n = 12) and western blotting (n = 22), the HBV surface protein, which is mainly comprised of the major form of HBV surface antigen, was greatly diminished in the tumors. However, LHBS was not significantly decreased in tumorous regions, suggesting that LHBS maintains its expression in cancer development. A cohort of 175 patients with HBV-related HCC who underwent curative hepatic resection was analyzed for pre-S gene mutations using Pre-S Gene Chip. Results of the multivariate regression analysis showed that the serum pre-S2 mutant level and the American Joint Committee on Cancer stage were the two main independent high-risk factors for recurrence. A Cox proportional hazards analysis also revealed a prediction model, which indicated the recurrence-free survival rate along with the time after surgery; this was developed and further validated in an independent HCC cohort. Receiver operating characteristic curve analysis revealed that the model showed close sensitivities in the main and validation cohorts (area under the curve values, 0.741 and 0.704, respectively). Conclusion: Unlike the major HBV surface antigen, LHBS is mostly expressed in the tumorous regions of HBV-induced HCC, indicating that it plays a unique role in tumor progression; the relative level of pre-S2 mutant in serum is, independently of tumor stage, an important high-risk marker for HCC recurrence after primary hepatic resection. (Hepatology 2018).
Authors: Peter A Revill; Thomas Tu; Hans J Netter; Lilly K W Yuen; Stephen A Locarnini; Margaret Littlejohn Journal: Nat Rev Gastroenterol Hepatol Date: 2020-05-28 Impact factor: 46.802