2014/12/3 上午12:32 Oasis, The Online Abstract Submission System
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Control/Tracking Number: 15-A-1375-AACR Activity: Abstract Submission
Current Date/Time: 12/2/2014 10:32:02 AM
Androgen Receptor Expression Reduces Post-Hepatectomy Surgery Recurrence Risks of Hepatocellular Carcinoma Short Title:
AR reduces HCC recurrence
Author Block: Wen-Lung Ma1, Pei-Yin Liao1, Chun-Chieh Yeh2, Long-Bin Jeng2, Hsueh-Chou Lai2, Shang-Feng Huang2, Fu-Ju Lei1. 1China Medical University, Taichung, Taiwan; 2China Medical University Hospital, Taichung, Taiwan
Abstract:
Introduction: Androgen Receptor (AR) promotes hepatocarcinogenesis, yet, suppresses HCC (hepatocellular carcinoma) progression of HCC mouse models. Yet, the translational value of AR expression in HCC patients is not clear. The CD90 membrane protein is cancer stem/progenitor cells (CSPC) marker, which can be detected in Circulating Tumor Cells (CTC). It's recognized as surgery HCC recurrence confounder. In this report, we examined the roles of AR expressions in post-hepatectomy HCC recurrence, and provide cellular and molecular insight to AR effect in HCC recurrence.
Methods: We detected AR vs. CD90 expressions in primary tumor and CTC of HCC patients whom subjected to hepatectomy surgery to associated with HCC recurrence. In addition, we delineated the cellular and molecular mechanisms in AR knockout (ARKO)-HCC model, as well as in human HCC cell lines. Furthermore, systems biological approach was also introduced to examine AR-mediated gene expression pathways enrichment.
Result: We found opposite association power of AR vs. CD90 that higher CD90 was related to higher risk; yet, higher AR was refer to lower risks of HCC recurrence. The mechanisms are summarized as follow:
1). AR suppresses CD90 through Histone 3H2A (H3H2A) acetylation: The AR vs. CD90 is reversely expressed in the specimens. The CD90+ cells increases in ARKO compared to that in wildtype (WT) mouse HCC. AR abolishes CD90 expression in two HCC cell lines, in which H3H2A upregulation and acetylation also noted. Knockdown of H3H2A could recover CD90 expression under AR effect.
2). AR reprogram gene expression to inhibit cell migration: AR suppresses HCC cell migration in an AR-level dependent manner with shifted gene expression pattern. Systems biological analysis revealed that low AR is related to cell-cycle enrichment gene settings; yet, shift to cell migration suppression setting while AR level increased.
3). AR promotes cell anoikis through facilitating cellular stress produced by resolving cytoskeletons (amorphosis) in circulation: AR promotes cell anoikis through a non-classical AR function, by which to activate PI3K/AKT- and ROCK-related cytoskeletal
rearrangement stress while the cells in anchorage independent condition.
Conclusion: To sum up, this report demonstrated that AR expressions could serves as prognostic marker for HCC recurrence. And there are three mechanisms involved: AR reduces CD90 population through epigenetic modification, AR inhibits cell migration through gene expression shift, and AR promote anoikis through increasing amorphosis stress.
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Author Disclosure Information: W. Ma: ; Taiwan Ministry Of Sciences and Technology. ; Taiwan National Health Research Institute. ; China Medical University. P. Liao: ; Taiwan National Research Institute. C. Yeh: ; China Medical University. L. Jeng: ; China Medical University Hospital. H. Lai: ; China Medical University Hospital. S. Huang: ; China Medical University Hospital. F. Lei: ; Taiwan Ministry Of Sciences and Technology.
Sponsor (Complete):
Category and Subclass (Complete): EN02-02 Hormone receptors and diagnosis/prognosis Research Type (Complete): Translational research
2014/12/3 上午12:32 Oasis, The Online Abstract Submission System
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Powered by OASIS, The Online Abstract Submission and Invitation System SM © 1996 - 2014 Coe-Truman Technologies, Inc. All rights reserved. Keywords/Indexing (Complete): Androgen receptor ; Hepatocellular carcinoma ; Recurrence Submission Details (Complete):
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