Long Noncoding RNA HOTAIR as an Independent Prognostic Marker in Cancer: A Meta-Analysis

PLoS One. 2014 Aug 26;9(8):e105538. doi: 10.1371/journal.pone.0105538. eCollection 2014.


Background: HOTAIR, a newly discovered long intergenic noncoding RNA (lincRNA), has been reported to be aberrantly expressed in many types of cancers. This meta-analysis summarizes its potential role as a biomarker in malignancy.

Methods: A quantitative meta-analysis was performed through a systematic search in Pubmed, Medline and Web of Science for eligible papers on the prognostic impact of HOTAIR in cancer from inception to Feb. 28, 2014. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to summarize the effect.

Results: Nineteen studies were included in the study, with a total of 2033 patients. A significant association was observed between high HOTAIR expression and poor overall survival (OS) in patients with cancer (pooled HR 2.22, 95% CI: 1.68-2.93). Place of residence (Asian or Western countries), type of cancer (digestive or non-digestive disease), sample size (more or less than 100), and paper quality (score more or less than 85%) did not alter the significant predictive value of HOTAIR in OS from various kinds of cancer but preoperative status did. By combining HRs from Cox multivariate analyses, we found that HOTAIR expression was an independent prognostic factor for cancer patients (pooled HR 2.26, 95% CI: 1.62-3.15). Subgroup analysis showed that HOTAIR abundance was an independent prognostic factor for cancer metastasis (HR 3.90, 95% CI: 2.25-6.74). For esophageal carcinoma, high HOTAIR expression was significantly associated with TNM stage (III/IV vs. I/II: OR 6.90, 95% CI: 2.81-16.9) without heterogeneity. In gastric cancer, HOTAIR expression was found to be significantly associated with lymph node metastases (present vs. absent: OR 4.47, 95% CI: 1.88-10.63) and vessel invasion (positive vs. negative: OR 2.88, 95% CI: 1.38-6.04) without obvious heterogeneity.

Conclusions: HOTAIR abundance may serve as a novel predictive factor for poor prognosis in different types of cancers in both Asian and Western countries.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / diagnosis*
  • Neoplasms / genetics*
  • Neoplasms / pathology
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Up-Regulation


  • Biomarkers, Tumor
  • HOTAIR long untranslated RNA, human
  • RNA, Long Noncoding

Grant support

This work was supported by the Natural Scientific Foundation of Guangdong Province (S2012040007685), Doctoral Program Foundation of Institutions of Higher Education of China (20120171120090) and National Natural Science Foundation of China (81301769). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.