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

BMC Gastroenterology

Research Article

Li-Xia Wang¹  Dong Yang¹  He Chen¹  Zhi-Jun Duan¹  Xiao-Sha Feng¹  Zhi-Feng Zhang¹  Qiu-Ping Zhang²  Yan-Ling Jin²  Zhi-Gang Sun²  Han Liu³  Pi-Xu Liu³ 

[1] Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, 116000, Dalian, Liaoning Province, China;Department of Pathology, The First Affiliated Hospital of Dalian Medical University, 116000, Dalian, Liaoning Province, China;Institute of Cancer Stem Cell, Dalian Medical University, 116000, Dalian, Liaoning Province, China;

关键词: Hepatocellular carcinoma;    Hexokinase-2;    Beta2-adrenergic receptor;    Prognosis;    Immunohistochemistry;   

DOI  :  10.1186/s12876-016-0474-8

 received in 2015-10-23, accepted in 2016-05-27,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundHexokinase-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.MethodsImmunohistochemistry 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.Results109 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).ConclusionHK2 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.

【 授权许可】

CC BY   
© The Author(s). 2016