Medical Oncology

, Volume 29, Issue 4, pp 2780–2792 | Cite as

Coexpression of Bcl-2 with epithelial–mesenchymal transition regulators is a prognostic indicator in hepatocellular carcinoma

  • Nan Zhao
  • Bao-cun Sun
  • Xiu-lan Zhao
  • Zhi-yong Liu
  • Tao Sun
  • Zhi-qiang Qiu
  • Qiang Gu
  • Na Che
  • Xue-yi Dong
Original Paper
First Online:
Received:
Accepted:

Abstract

The anti-apoptosis factor Bcl-2 is known to contribute to tumorigenesis and metastasis. Epithelial–mesenchymal transition (EMT) may also participate in tumor invasion and metastasis. This study investigated the relationship between coexpression profiles of Bcl-2 and EMT regulators in hepatocellular carcinoma (HCC) tumor samples and clinical outcome. The nuclear (Nu) and cytoplasmic (Cyt) expression of Bcl-2 and the EMT regulators Twist-1, Twist-2, and Snail were determined by immunohistochemical staining in tumor tissue isolated from 97 HCC patients. The clinical prognostic values of both individual protein expression and various expression combinations were investigated using univariate and multivariate survival analysis. Results showed that patients with nuclear expression of Bcl-2 had worse clinical outcomes than patients exhibiting cytoplasmic expression. Overall survival was significantly shorter in HCC patients individually expressing Bcl-2-Nu, Twist-1-Nu, Twist-1-Cyt, and Snail (all P < 0.05). Patients coexpressing Bcl-2-Nu with Twist-1-Nu, Twist-1-Cyt, Twist-2, or Snail had even worse prognoses than those expressing no biomarker or any one biomarker alone (all P < 0.05). Multivariate analysis showed that HCC patients coexpressing Bcl-2-Nu with Twist-1-Cyt had the worst prognosis. This study provides clinical evidence that nuclear expression of Bcl-2 combined with cytoplasmic expression of Twist-1 is a predictor of very poor prognosis in HCC. Coexpression profiles of Bcl-2 and EMT regulators might aid in the selection of the most efficacious therapy for patients with HCC.

Keywords

Hepatocellular carcinoma Bcl-2 EMT regulators Protein-coexpression profiles Prognosis 
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Notes

Acknowledgments

This study was supported by the Key Project of National Nature Science Foundation of China (No. 30830049), Project of National Nature Science Foundation of China (No.81173091 and No.81172046), the co-operation of China–Sweden (No. 09ZCZDSF04400), the Research Fund for the Doctoral Program of High Education (No.20111202110010) and the “211 Project” Graduate Innovation Grant of Tianjin Medical University (No.146-200002).

Conflict of interest

All authors have read and approved the article before submission to your journal. There is no conflict of interest of any authors in relation to the submission.

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Nan Zhao
    • 1
  • Bao-cun Sun
    • 1
    • 2
  • Xiu-lan Zhao
    • 1
  • Zhi-yong Liu
    • 2
  • Tao Sun
    • 1
  • Zhi-qiang Qiu
    • 2
  • Qiang Gu
    • 1
  • Na Che
    • 1
  • Xue-yi Dong
    • 1
  1. 1.Department of PathologyTianjin Medical UniversityTianjinPeople’s Republic of China
  2. 2.Department of Pathology, Cancer HospitalTianjin Medical UniversityTianjinPeople’s Republic of China

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