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Breast Cancer Research and Treatment

, Volume 136, Issue 3, pp 875–883 | Cite as

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

  • Lingeng Lu
  • Guangjian Zhu
  • Chong Zhang
  • Qian Deng
  • Dionyssios Katsaros
  • Susan T. Mayne
  • Harvey A. Risch
  • Lina Mu
  • Emilie Marion Canuto
  • Gianluca Gregori
  • Chiara Benedetto
  • Herbert Yu
Epidemiology

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.

Keywords

Large non-coding RNA DNA methylation Gene expression Breast cancer Prognosis 

Notes

Conflict of interest

The authors declare that there are no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Lingeng Lu
    • 1
  • Guangjian Zhu
    • 1
    • 2
  • Chong Zhang
    • 1
    • 3
  • Qian Deng
    • 1
    • 4
  • Dionyssios Katsaros
    • 5
  • Susan T. Mayne
    • 1
  • Harvey A. Risch
    • 1
  • Lina Mu
    • 6
  • Emilie Marion Canuto
    • 5
  • Gianluca Gregori
    • 5
  • Chiara Benedetto
    • 5
  • Herbert Yu
    • 1
    • 7
  1. 1.Department of Chronic Disease Epidemiology, Yale Cancer CenterYale School of Public HealthNew HavenUSA
  2. 2.Gansu Provincial Academy of Medical ScienceGansu Provincial Tumor HospitalLanzhouChina
  3. 3.Gansu Provincial Hospital for the Protection of Mother and Baby’s HealthLanzhouChina
  4. 4.National Center for Chronic and Non-communicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina
  5. 5.Department of Gynecologic OncologyAzienda Ospedaliera OIRM-S.ANNA and University of TorinoTurinItaly
  6. 6.Department of Social and Preventive MedicineUniversity at Buffalo, The State University of New YorkBuffaloUSA
  7. 7.Epidemiology ProgramUniversity of Hawaii Cancer CenterHonoluluUSA

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