Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation

Ann Surg Oncol. 2011 May;18(5):1243-50. doi: 10.1245/s10434-011-1581-y. Epub 2011 Feb 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Blotting, Western
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / therapy*
  • Cell Proliferation
  • Cells, Cultured
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / therapy
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / therapy
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Untranslated / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • RNA, Untranslated