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Article: Glutathione S-transferase A2 promotes hepatocellular carcinoma recurrence after liver transplantation through modulating reactive oxygen species metabolism

TitleGlutathione S-transferase A2 promotes hepatocellular carcinoma recurrence after liver transplantation through modulating reactive oxygen species metabolism
Authors
Issue Date2021
PublisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/cddiscovery/
Citation
Cell Death Discovery, 2021, v. 7, p. article no. 188 How to Cite?
AbstractHepatocellular carcinoma (HCC) recurrence after liver transplantation remains a significant clinical problem. Ischemia-reperfusion injury (IRI) occurred inevitably at the early phase after liver transplantation (LT) spawns a significant risk of HCC recurrence. However, their linkage and IRI-derived risk factors for HCC recurrence remain exclusive. Understanding the mechanism of post-transplantation hepatic injury could provide new strategies to prevent the later event of HCC recurrence. We demonstrated that glutathione S-transferase A2 (GSTA2) expression was significantly associated with early phase hepatic and systemic injury and ROS level after liver transplantation. Early phase circulating GSTA2 (EPCGSTA2) protein was a significant predictor of HCC recurrence and survival. Heterogeneous single nucleotide polymorphism at G335C of GSTA2 was significantly associated with poor survival of HCC recipients. Enhancement of GSTA2 could protect HCC cells against H2O2-induced cell death by compensating for the elevated ROS stress. We also demonstrated that GSTA2 played crucial roles in regulating the ROS-associated JNK and AKT signaling pathways and ROS metabolism in HCCs in responding to a dynamic ROS environment. Functionally, endogenous or exogenous upregulation of GSTA2 could promote HCC growth and invasion through activating the epithelial-mesenchymal-transition process. Targeted inhibition of GSTA2 could suppress HCC growth and metastasis. In conclusion, GSTA2 could be a novel prognostic and therapeutic target to combat HCC recurrence after liver transplantation.
Persistent Identifierhttp://hdl.handle.net/10722/301970
ISSN
2023 Impact Factor: 6.1
2023 SCImago Journal Rankings: 1.668
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorNg, KTP-
dc.contributor.authorYeung, WHO-
dc.contributor.authorLAM, YF-
dc.contributor.authorLiu, J-
dc.contributor.authorLiu, H-
dc.contributor.authorPANG, L-
dc.contributor.authorYANG, XX-
dc.contributor.authorZHU, J-
dc.contributor.authorZHANG, W-
dc.contributor.authorLau, MYH-
dc.contributor.authorQIU, W-
dc.contributor.authorShiu, HC-
dc.contributor.authorLai, MK-
dc.contributor.authorLo, CM-
dc.contributor.authorMan, K-
dc.date.accessioned2021-08-21T03:29:39Z-
dc.date.available2021-08-21T03:29:39Z-
dc.date.issued2021-
dc.identifier.citationCell Death Discovery, 2021, v. 7, p. article no. 188-
dc.identifier.issn2058-7716-
dc.identifier.urihttp://hdl.handle.net/10722/301970-
dc.description.abstractHepatocellular carcinoma (HCC) recurrence after liver transplantation remains a significant clinical problem. Ischemia-reperfusion injury (IRI) occurred inevitably at the early phase after liver transplantation (LT) spawns a significant risk of HCC recurrence. However, their linkage and IRI-derived risk factors for HCC recurrence remain exclusive. Understanding the mechanism of post-transplantation hepatic injury could provide new strategies to prevent the later event of HCC recurrence. We demonstrated that glutathione S-transferase A2 (GSTA2) expression was significantly associated with early phase hepatic and systemic injury and ROS level after liver transplantation. Early phase circulating GSTA2 (EPCGSTA2) protein was a significant predictor of HCC recurrence and survival. Heterogeneous single nucleotide polymorphism at G335C of GSTA2 was significantly associated with poor survival of HCC recipients. Enhancement of GSTA2 could protect HCC cells against H2O2-induced cell death by compensating for the elevated ROS stress. We also demonstrated that GSTA2 played crucial roles in regulating the ROS-associated JNK and AKT signaling pathways and ROS metabolism in HCCs in responding to a dynamic ROS environment. Functionally, endogenous or exogenous upregulation of GSTA2 could promote HCC growth and invasion through activating the epithelial-mesenchymal-transition process. Targeted inhibition of GSTA2 could suppress HCC growth and metastasis. In conclusion, GSTA2 could be a novel prognostic and therapeutic target to combat HCC recurrence after liver transplantation.-
dc.languageeng-
dc.publisherNature Publishing Group: Open Access Journals. The Journal's web site is located at http://www.nature.com/cddiscovery/-
dc.relation.ispartofCell Death Discovery-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleGlutathione S-transferase A2 promotes hepatocellular carcinoma recurrence after liver transplantation through modulating reactive oxygen species metabolism-
dc.typeArticle-
dc.identifier.emailNg, KTP: ledodes@hku.hk-
dc.identifier.emailYeung, WHO: why21@hku.hk-
dc.identifier.emailLiu, H: liuhui25@hku.hk-
dc.identifier.emailShiu, HC: hoicshiu@hku.hk-
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hk-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.authorityNg, KTP=rp01720-
dc.identifier.authorityLo, CM=rp00412-
dc.identifier.authorityMan, K=rp00417-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41420-021-00569-y-
dc.identifier.pmid34290233-
dc.identifier.pmcidPMC8295304-
dc.identifier.scopuseid_2-s2.0-85110944128-
dc.identifier.hkuros324179-
dc.identifier.volume7-
dc.identifier.spagearticle no. 188-
dc.identifier.epagearticle no. 188-
dc.identifier.isiWOS:000677614000002-
dc.publisher.placeUnited Kingdom-

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