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Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection

BACKGROUND: Hexokinase-2 (HK2) and Beta2-adrenergic receptor (Beta2AR) are overexpressed in hepatocellular carcinoma (HCC) tissues and associated with poor prognosis. However, the synergistic effect of HK2 and Beta2AR in HCC prognosis is not elucidated. The present study aims to investigate the asso...

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Autores principales: Zhang, Zhi-Feng, Feng, Xiao-Sha, Chen, He, Duan, Zhi-Jun, Wang, Li-Xia, Yang, Dong, Liu, Pi-Xu, Zhang, Qiu-Ping, Jin, Yan-Ling, Sun, Zhi-Gang, Liu, Han
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891884/
https://www.ncbi.nlm.nih.gov/pubmed/27255554
http://dx.doi.org/10.1186/s12876-016-0474-8
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author Zhang, Zhi-Feng
Feng, Xiao-Sha
Chen, He
Duan, Zhi-Jun
Wang, Li-Xia
Yang, Dong
Liu, Pi-Xu
Zhang, Qiu-Ping
Jin, Yan-Ling
Sun, Zhi-Gang
Liu, Han
author_facet Zhang, Zhi-Feng
Feng, Xiao-Sha
Chen, He
Duan, Zhi-Jun
Wang, Li-Xia
Yang, Dong
Liu, Pi-Xu
Zhang, Qiu-Ping
Jin, Yan-Ling
Sun, Zhi-Gang
Liu, Han
author_sort Zhang, Zhi-Feng
collection PubMed
description BACKGROUND: Hexokinase-2 (HK2) and Beta2-adrenergic receptor (Beta2AR) are overexpressed in hepatocellular carcinoma (HCC) tissues and associated with poor prognosis. However, the synergistic effect of HK2 and Beta2AR in HCC prognosis is not elucidated. The present study aims to investigate the association between HK2 and Beta2AR expressions in HCC tissues, and to evaluate the synergistic effect of HK2 and Beta2AR in HCC prognosis. METHODS: Immunohistochemistry of HK2 and Beta2AR was performed on 155 paraffin embedded HCC samples retrieved from the archives of pathology department. Corresponding clinical data and prognostic data were collected through searching medical record systems, death registration systems and interviews with patient families. Spearman correlation test was performed to evaluate the association between HK2 and Beta2AR expression. Kaplan-Meier survival curves and Cox regressions were employed to evaluate HK2 and Beta2AR expression in HCC prognosis, respectively and synergistically. RESULTS: 109 of 155 HCC patients reached the death point, the survival time of HCC patients was 46.23 ± 31.01 months after curative surgical resections of HCC. Kaplan-Meier survival analysis showed that large tumor size (more than 5 cm) (hazard ratio (HR) = 8.42, 95 % confidence interval (CI) = 3.81–18.59, P < 0.0001), advanced TNM stage (III and IV stages) (HR = 2.09, 95%CI = 1.21–3.62, P < 0.001) and AFP more than 20 μg/L (HR = 1.49, 95%CI = 1.02–2.18, P = 0.0302) were predictors for poor prognosis. HK2 and Beta2AR positive expression was detected in 66 (42.58) and 122 (78.71 %) HCC samples respectively. In univariate analysis, HK2(+) (HR = 2.70, 95%CI = 1.76–4.15, P < 0.0001) and Beta2AR(+) (HR = 4.61, 96%CI = 3.14–6.76, P < 0.0001) were associated with poor prognosis. In multivariate analysis, HK2(+) (P < 0.0001) and Beta2AR(+) (P < 0.0001) were also associated with poor prognosis. HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(−)/Beta2AR(−) in both univariate analysis (HR = 4.69, 95%CI = 2.91–7.57, P < 0.0001) and multivariate analysis (P < 0.0001). HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(−)/Beta2AR(+) in both univariate analysis (HR = 1.76, 95%CI = 1.17–2.64, P = 0.003) and multivariate analysis (P = 0.004). CONCLUSION: HK2 and Beta2AR play important roles in HCC progression. HK2 and Beta2AR expression in HCC is correlated positively. Beta2AR may increase HCC invasion and metastasis in collaboration with HK2. HK2 and Beta2AR can predict HCC prognosis both independently and synergistically.
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spelling pubmed-48918842016-06-04 Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection Zhang, Zhi-Feng Feng, Xiao-Sha Chen, He Duan, Zhi-Jun Wang, Li-Xia Yang, Dong Liu, Pi-Xu Zhang, Qiu-Ping Jin, Yan-Ling Sun, Zhi-Gang Liu, Han BMC Gastroenterol Research Article BACKGROUND: Hexokinase-2 (HK2) and Beta2-adrenergic receptor (Beta2AR) are overexpressed in hepatocellular carcinoma (HCC) tissues and associated with poor prognosis. However, the synergistic effect of HK2 and Beta2AR in HCC prognosis is not elucidated. The present study aims to investigate the association between HK2 and Beta2AR expressions in HCC tissues, and to evaluate the synergistic effect of HK2 and Beta2AR in HCC prognosis. METHODS: Immunohistochemistry of HK2 and Beta2AR was performed on 155 paraffin embedded HCC samples retrieved from the archives of pathology department. Corresponding clinical data and prognostic data were collected through searching medical record systems, death registration systems and interviews with patient families. Spearman correlation test was performed to evaluate the association between HK2 and Beta2AR expression. Kaplan-Meier survival curves and Cox regressions were employed to evaluate HK2 and Beta2AR expression in HCC prognosis, respectively and synergistically. RESULTS: 109 of 155 HCC patients reached the death point, the survival time of HCC patients was 46.23 ± 31.01 months after curative surgical resections of HCC. Kaplan-Meier survival analysis showed that large tumor size (more than 5 cm) (hazard ratio (HR) = 8.42, 95 % confidence interval (CI) = 3.81–18.59, P < 0.0001), advanced TNM stage (III and IV stages) (HR = 2.09, 95%CI = 1.21–3.62, P < 0.001) and AFP more than 20 μg/L (HR = 1.49, 95%CI = 1.02–2.18, P = 0.0302) were predictors for poor prognosis. HK2 and Beta2AR positive expression was detected in 66 (42.58) and 122 (78.71 %) HCC samples respectively. In univariate analysis, HK2(+) (HR = 2.70, 95%CI = 1.76–4.15, P < 0.0001) and Beta2AR(+) (HR = 4.61, 96%CI = 3.14–6.76, P < 0.0001) were associated with poor prognosis. In multivariate analysis, HK2(+) (P < 0.0001) and Beta2AR(+) (P < 0.0001) were also associated with poor prognosis. HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(−)/Beta2AR(−) in both univariate analysis (HR = 4.69, 95%CI = 2.91–7.57, P < 0.0001) and multivariate analysis (P < 0.0001). HK2(+)/Beta2AR(+) in HCC samples had poorer prognosis compared with HK2(−)/Beta2AR(+) in both univariate analysis (HR = 1.76, 95%CI = 1.17–2.64, P = 0.003) and multivariate analysis (P = 0.004). CONCLUSION: HK2 and Beta2AR play important roles in HCC progression. HK2 and Beta2AR expression in HCC is correlated positively. Beta2AR may increase HCC invasion and metastasis in collaboration with HK2. HK2 and Beta2AR can predict HCC prognosis both independently and synergistically. BioMed Central 2016-06-03 /pmc/articles/PMC4891884/ /pubmed/27255554 http://dx.doi.org/10.1186/s12876-016-0474-8 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhang, Zhi-Feng
Feng, Xiao-Sha
Chen, He
Duan, Zhi-Jun
Wang, Li-Xia
Yang, Dong
Liu, Pi-Xu
Zhang, Qiu-Ping
Jin, Yan-Ling
Sun, Zhi-Gang
Liu, Han
Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection
title Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection
title_full Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection
title_fullStr Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection
title_full_unstemmed Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection
title_short Prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection
title_sort prognostic significance of synergistic hexokinase-2 and beta2-adrenergic receptor expression in human hepatocelluar carcinoma after curative resection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891884/
https://www.ncbi.nlm.nih.gov/pubmed/27255554
http://dx.doi.org/10.1186/s12876-016-0474-8
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