The Beta2-Adrenergic Receptor is a Potential Prognostic Biomarker for Human Hepatocellular Carcinoma After Curative Resection

Chen, Dongtai; Xing, Wei; Hong, Jian; Wang, Meibing; Huang, Yang; Zhu, Cuizhen; Yuan, Yunfei; Zeng, Weian

doi:10.1245/s10434-012-2396-1

Cited by 36 publications

(29 citation statements)

References 29 publications

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“…High expression of Beta2AR may play a role in the canceration of injured hepatocytes, and may represent high grade of malignancy of HCC. So high expression of Beta2AR in HCC tissues is proposed be a biomarker for poor prognosis, which is supported by a previous survival study of HCC with immunohistochemistry [ 10 ].…”

Section: Introductionmentioning

confidence: 61%

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

et al. 2016

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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.

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Section: Introductionmentioning

confidence: 61%

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

et al. 2016

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“…To evaluate IHC staining of NEK2/β-catenin in the nuclear and cytoplasmic regions, the expression of NEK2/β-catenin was scored as absent staining (-), weak staining (+), moderate staining (++) and strong staining (+++). In the present study, we characterize a low (-/+) score of NEK2/β-catenin as 'NEK2/β-catenin negative' and a high (++/+++) score of NEK2/β-catenin as 'NEK2/β-catenin positive', respectively (15,16). Assessments of the staining were scored in a double-blinded manner by two experienced pathologists.…”

Section: Methodsmentioning

confidence: 95%

NEK2 regulates stem-like properties and predicts poor prognosis in hepatocellular carcinoma

et al. 2016

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NEK2 has been estimated to play an important role in cancer progression. However, its relevance in hepatocellular carcinoma (HCC) has not yet been explored. Immunohistochemistry revealed NEK2 expression was upregulated in HCC. NEK2-positive hepatocellular carcinoma patients were associated with poor prognosis after surgery compared with NEK2-negative patients based on Kaplan-Meier curves. Deletion of NEK2 reduced self-renewal properties and chemotherapeutic resistance, and decreased the stemness associated genes in cell lines. NEK2 was associated with unfavorable outcomes in HCC patients, and was revealed to regulate self-renewal property by means of Wnt/β-catenin signaling, and chemotherapeutic resistance by preferential regulation of the expression of ABCG2 and ALDH1A1 in HCC cells.

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“…Despite the remarkable advances in diagnostic and therapeutic techniques, prognosis of HCC still remains extremely poor, ranking as the third leading cause of cancer-related death worldwide [ 1 ]. Therefore, numerous studies have focused on screening for novel diagnostic and prognostic biomarkers as well as therapeutic targets in HCC [ 5 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of KIF23 variant 1 expression and relevance as a novel prognostic factor in patients with hepatocellular carcinoma

et al. 2015

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BackgroundKIF23 (kinesin family member 23) is a kinesin-like motor protein and plays an important role in cytokinesis. In search for genes associated with hepatocellular carcinoma (HCC) by cDNA microarray, we found that KIF23 was upregulated in HCC tissues. At present, much less is known about its expression and functions in tumor cells. In this work, we aimed to investigate the expression of KIF23 in HCC and the correlation between its expression and clinical features.MethodsTotal RNA was extracted from 16 HCC and paired adjacent non-cancerous tissues. The expressions of the two KIF23 splice variants (KIF23 V1 and KIF23 V2) in normal and HCC tissues were determined by reverse transcriptase polymerase chain reaction (RT-PCR). Polyclonal antibody specific to KIF23 V1 was prepared, and the specificity of the antibody was confirmed by siRNA knockdown and Western blotting experiments. KIF23 protein expression in HCC was examined by immunohistochemistry staining with anti-KIF23 V1 or anti-KIF23 (commercially available for recognizing both KIF23 V1 and V2) antibodies, respectively. Univariate and Multivariate Cox regression analyses were used to determine the correlation between KIF23 protein expression and overall survival of HCC patients.ResultsThe two splicing variants of KIF23 mRNA were not detected in normal liver tissue by RT-PCR, but they were aberrantly expressed in HCC tissues. Immunohistochemistry staining with anti-KIF23 V1 antibody revealed that KIF23 V1 was mainly distributed in the nucleus, whereas the positive staining signals were predominantly in the cytoplasm when using anti-KIF23 antibody, suggesting that KIF23 V2 might localize in the cytoplasm of HCC cells. KIF23 V1 protein was detected in 57.6 % (83/144) HCC patients and the mean H-score was 42, while KIF23 V2 was detected in 94.4 % (135/143) HCC samples and the mean H-score was 68. Follow-up study showed that HCC patients with expression of KIF23 V1 had a longer 5-year survival (p = 0.0052), however, expression of KIF23 V2 protein did not associate with 3- and 5-year survival.ConclusionIn this study we show for the first time that KIF23 V1 and V2 have different localizations in HCC cells. Furthermore, KIF23 V1 protein expression might be a marker of longer overall survival in HCC patients.

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The Beta2-Adrenergic Receptor is a Potential Prognostic Biomarker for Human Hepatocellular Carcinoma After Curative Resection

Abstract: The Beta2-AR is a potential prognostic biomarker for survival and tumor recurrence in HCC patients after curative resection.

Cited by 36 publications

References 29 publications

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

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

NEK2 regulates stem-like properties and predicts poor prognosis in hepatocellular carcinoma

Evaluation of KIF23 variant 1 expression and relevance as a novel prognostic factor in patients with hepatocellular carcinoma

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