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Up-regulation of microRNA-155 promotes cancer cell invasion and predicts poor survival of hepatocellular carcinoma following liver transplantation

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Abstract

Purpose

MicroRNAs play important roles in cancer development, progression, and metastasis. The aim of this study was to determine whether altered microRNA-155 expression is associated with hepatocellular carcinoma (HCC) recurrence and prognosis following orthotopic liver transplantation (OLT).

Methods

Tissue specimens from 100 HCC patients following OLT were recruited. MicroRNA-155 expression levels were detected using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Kaplan–Meier and Cox proportional regression analyses were utilized to determine the association of microRNA-155 expression with survival of patients. MicroRNA-155 expression levels of two HCC cell lines (HepG2 and SMMC-7721) and normal liver tissue were quantified using qRT-PCR. The potential function of miR-155 on invasiveness was evaluated in the above HCC cell lines.

Results

We found that microRNA-155 expression levels were high in tumor tissues in patients with post-OLT HCC recurrence (n = 45) compared with those in patients with non-recurrence (n = 55) (P = 0.001) and correlated with micro-vascular invasion of HCC tissue samples (P = 0.001). Patients with higher miR-155 expression had significantly poorer recurrence-free survival (RFS, log rank P < 0.001) and overall survival (OS, log rank P < 0.001). Multivariate analysis revealed that high miR-155 expression was an independent predictor of poor prognosis (HR 2.748, P = 0.001 for RFS; HR 5.752, P < 0.001 for OS). In addition, the invasiveness of HCC cells was significantly increased by higher microRNA-155 expression.

Conclusions

MicroRNA-155 is a candidate oncogenic microRNA and plays an important role in promoting HCC cells invasion. Our findings suggest that microRNA-155 may serve as a novel biomarker for tumor recurrence and survival of HCC patients following OLT.

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Acknowledgments

This study was supported by a grant from the National Key Technology R&D Program (#2008BAI60B03).

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Authors and Affiliations

  1. Department of General Surgery, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, 100 Haining Road, Shanghai, 200080, China

    Zhong-Bo Han, Hong-Yuan Chen, Jun-Wei Fan, Jun-Yi Wu & Zhi-Hai Peng

  2. Department of Pathology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200080, China

    Hua-Mei Tang

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  1. Zhong-Bo Han
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  2. Hong-Yuan Chen
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Correspondence to Zhi-Hai Peng.

Additional information

Zhong-Bo Han and Hong-Yuan Chen contributed equally to this work.

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Han, ZB., Chen, HY., Fan, JW. et al. Up-regulation of microRNA-155 promotes cancer cell invasion and predicts poor survival of hepatocellular carcinoma following liver transplantation. J Cancer Res Clin Oncol 138, 153–161 (2012). https://doi.org/10.1007/s00432-011-1076-z

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  • DOI: https://doi.org/10.1007/s00432-011-1076-z

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