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Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer

  • Epidemiology
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Abstract

Large noncoding RNA HOTAIR, transcribed from the antisense strand of HOXC12, interacts with Polycomb Repressive Complex 2 (PRC2) in the regulation of gene activities. Recent work suggests that it may have effects on breast cancer progression and survival. We evaluated HOTAIR expression and the methylation status of its downstream intergenic CpG island in primary breast cancers, and examined associations of these factors with clinical and pathologic features and patient survival. HOTAIR expression and DNA methylation were analyzed in tissue from 348 primary breast cancers with quantitative RT-PCR and methylation-specific PCR, respectively. HOTAIR expression and methylation varied widely in the tissues. A positive correlation was found between DNA methylation and HOTAIR expression. Methylation was associated with unfavorable disease characteristics, whereas no significant associations were found between HOTAIR expression and clinical or pathologic features. In multivariate, but not in univariate, Cox proportional hazard regression models, patients with high HOTAIR expression had lower risks of relapse and mortality than those with low HOTAIR expression. These findings suggest that the intergenic DNA methylation may have important biologic relevance in regulating HOTAIR expression, and that HOTAIR expression may not be an independent prognostic marker in breast cancer, but needs further validation in independent studies.

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Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Author notes

  1. Herbert Yu

    Present address: Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, 96813, USA

Authors and Affiliations

  1. Department of Chronic Disease Epidemiology, Yale Cancer Center, Yale School of Public Health, 60 College Street, New Haven, CT, 06520-8034, USA

    Lingeng Lu, Guangjian Zhu, Chong Zhang, Qian Deng, Susan T. Mayne, Harvey A. Risch & Herbert Yu

  2. Gansu Provincial Academy of Medical Science, Gansu Provincial Tumor Hospital, Lanzhou, China

    Guangjian Zhu

  3. Gansu Provincial Hospital for the Protection of Mother and Baby’s Health, Lanzhou, China

    Chong Zhang

  4. National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China

    Qian Deng

  5. Department of Gynecologic Oncology, Azienda Ospedaliera OIRM-S.ANNA and University of Torino, Turin, Italy

    Dionyssios Katsaros, Emilie Marion Canuto, Gianluca Gregori & Chiara Benedetto

  6. Department of Social and Preventive Medicine, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA

    Lina Mu

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  1. Lingeng Lu
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Correspondence to Lingeng Lu.

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Lu, L., Zhu, G., Zhang, C. et al. Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer. Breast Cancer Res Treat 136, 875–883 (2012). https://doi.org/10.1007/s10549-012-2314-z

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  • DOI: https://doi.org/10.1007/s10549-012-2314-z

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