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

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The beta2-adrenergic receptor (Beta2-AR) is overexpressed and highly associated with poor prognosis in many malignancies. Nevertheless, the role of Beta2-AR in hepatocellular carcinoma (HCC) has not been thoroughly elucidated. The aim of this study is to investigate the expression of Beta2-AR and its clinicopathological/prognostic value in HCC patients after curative resection.

Materials and Methods

Semiquantitative reverse transcription PCR (RT-PCR) and real-time quantitative PCR (qPCR) were used to measure Beta2-AR RNA expression in 60 pairs of HCC tumors and matched nontumorous tissues. Beta2-AR expression was detected in HCC cell lines by Western blot analysis. Furthermore, we investigated Beta2-AR expression in correlation with the clinicopathological features and analyzed the potential prognostic significance of Beta2-AR in 192 HCC patients by immunohistochemistry (IHC).

Results

Upregulation of Beta2-AR mRNA was significantly higher in HCC tumor tissues than in their paired nontumorous liver specimens. The expression of Beta2-AR protein was detected in five HCC cell lines. Positive Beta2-AR protein expression was significantly associated with a high α-fetoprotein (AFP) level (P = 0.001), large tumor size (P < 0.001), tumor encapsulation (P = 0.002), vascular invasion (P = 0.004), microsatellite formation (P = 0.002), and poor differentiation (P < 0.001). In univariate and multivariate analyses, Beta2-AR was an excellent predictive factor for both recurrence-free survival and overall survival (OS). Beta2-AR expression status was associated with poor prognosis independent of AFP, tumor-node-metastasis stage and Edmondson stage.

Conclusions

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

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Acknowledgment

This work was supported by the National Natural Science Foundation of China (30972849).

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Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

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

  2. Department of Anesthesiology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China

    Dongtai Chen MD, Wei Xing MD, Meibing Wang MD, Yang Huang MD, Cuizhen Zhu MD & Weian Zeng MD, PhD

  3. Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

    Jian Hong MD, PhD & Yunfei Yuan MD

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  1. Dongtai Chen MD
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Correspondence to Weian Zeng MD, PhD.

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Dongtai Chen and Wei Xing contributed equally to this work.

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10434_2012_2396_MOESM1_ESM.jpg

Supplementary FIG. 1: Expression of Beta2-AR mRNA in HCC.Overexpression of Beta2-AR was detected in 60 pairs of HCC tumor(T) and matched nontumorous tissues (NT) by q-PCR. (JPG 12.3 mb)

10434_2012_2396_MOESM2_ESM.jpg

Supplementary FIG. 2: Beta2-AR is overexpressed in HCC.Representative images of Beta2-AR expression in HCC tumor (T) and matched nontumorous tissues (NT) detected by immunohistochemistry, Original magnification, ×100. Positive staining (Left) was detected in tumor tissues (T), negative staining (Right) was detected in matched nontumorous tissues (NT), Original magnification, ×200. (JPG 3.44 mb)

Supplementary material 3 (DOC 28 kb)

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Chen, D., Xing, W., Hong, J. et al. The Beta2-Adrenergic Receptor is a Potential Prognostic Biomarker for Human Hepatocellular Carcinoma After Curative Resection. Ann Surg Oncol 19, 3556–3565 (2012). https://doi.org/10.1245/s10434-012-2396-1

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  • DOI: https://doi.org/10.1245/s10434-012-2396-1

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