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Overexpression of Long Non-coding RNA HOTAIR Predicts Tumor Recurrence in Hepatocellular Carcinoma Patients Following Liver Transplantation

Annals of Surgical Oncology volume 18, pages 1243–1250 (2011)Cite this article

Abstract

Background

The long noncoding RNA HOTAIR has been reported as a poor prognostic biomarker in patients with breast cancer. The aim of the present study is to examine the expression pattern of HOTAIR in hepatocellular carcinoma (HCC) and its clinical significance as well as its biological role in tumor progression.

Materials and Methods

We examined the expression of HOTAIR in 110 HCC samples using real-time reverse transcription-polymerase chain reaction and analyzed its correlation with clinical parameters and prognosis in 60 HCC patients that have undergone liver transplantation (LT). Suppression of HOTAIR using siRNA was performed to explore its roles in tumor progression.

Results

The expression level of HOTAIR in cancer tissues was higher than in adjacent noncancerous tissues. High expression level of HOTAIR was an independent prognostic factor for predicting HCC recurrence in LT patients (P = .001, hazard ratio, 3.564). Furthermore, in patients exceeding the Milan criteria, those with a high expression level of HOTAIR revealed a significantly shorter recurrence-free survival. Moreover, siRNA suppression of HOTAIR in a liver cancer cell line reduced cell viability and cell invasion, sensitized TNF-α induced apoptosis, and increased the chemotherapeutic sensitivity of cancer cells to cisplatin and doxorubicin.

Conclusions

The high expression level of HOTAIR in HCC could be a candidate biomarker for predicting tumor recurrence in HCC patients who have undergone liver transplant therapy and might be a potential therapeutic target.

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Acknowledgment

This study was supported by the Major National S&T Program (2008ZX10002-026) and National Key Technology Support Program (2008BAI60B03). We thank the surgeons and nurses who kindly facilitate the recruitment and collection of patient information.

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Affiliations

  1. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, Zhejiang, China

    Zhe Yang MD, Lin Zhou PhD, Li-Ming Wu PhD, Ming-Chun Lai MD, Hai-Yang Xie MD, Feng Zhang PhD & Shu-Sen Zheng PhD, MD, FACS

  2. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

    Zhe Yang MD, Lin Zhou PhD, Li-Ming Wu PhD, Ming-Chun Lai MD, Hai-Yang Xie MD, Feng Zhang PhD & Shu-Sen Zheng PhD, MD, FACS

Authors
  1. Zhe Yang MD
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  2. Lin Zhou PhD
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  3. Li-Ming Wu PhD
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  4. Ming-Chun Lai MD
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  5. Hai-Yang Xie MD
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  6. Feng Zhang PhD
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  7. Shu-Sen Zheng PhD, MD, FACS
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Corresponding author

Correspondence to Shu-Sen Zheng PhD, MD, FACS.

Additional information

Z. Yang, L. Zhou, and L.-M. Wu contributed equally to this work.

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10434_2011_1581_MOESM1_ESM.eps

Supplementary material 1 (A) Kaplan-Meier curves estimate the recurrence-free survival rates according to the expression of HOTAIR combined with Milan criteria in 60 HCC patients who underwent LT. (B) Kaplan-Meier curves estimates the recurrence-free survival rates according to the expression of HOTAIR in 24 HCC patients who underwent hepatic resection (EPS 829 kb)

Supplementary material 2 (DOCX 29 kb)

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Yang, Z., Zhou, L., Wu, LM. et al. Overexpression of Long Non-coding RNA HOTAIR Predicts Tumor Recurrence in Hepatocellular Carcinoma Patients Following Liver Transplantation. Ann Surg Oncol 18, 1243–1250 (2011). https://doi.org/10.1245/s10434-011-1581-y

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  • DOI: https://doi.org/10.1245/s10434-011-1581-y

Keywords

  • HepG2 Cell
  • Milan Criterion
  • Adjacent Noncancerous Tissue
  • HOTAIR Expression
  • Liver Cancer Cell Line