Breast Cancer Research and Treatment

, Volume 154, Issue 3, pp 473–482 | Cite as

LINC00472 expression is regulated by promoter methylation and associated with disease-free survival in patients with grade 2 breast cancer

  • Yi Shen
  • Zhanwei Wang
  • Lenora WM Loo
  • Yan Ni
  • Wei Jia
  • Peiwen Fei
  • Harvey A. Risch
  • Dionyssios Katsaros
  • Herbert Yu
Preclinical study

Abstract

Long non-coding RNAs (lncRNAs) are a class of newly recognized DNA transcripts that have diverse biological activities. Dysregulation of lncRNAs may be involved in many pathogenic processes including cancer. Recently, we found an intergenic lncRNA, LINC00472, whose expression was correlated with breast cancer progression and patient survival. Our findings were consistent across multiple clinical datasets and supported by results from in vitro experiments. To evaluate further the role of LINC00472 in breast cancer, we used various online databases to investigate possible mechanisms that might affect LINC00472 expression in breast cancer. We also analyzed associations of LINC00472 with estrogen receptor, tumor grade, and molecular subtypes in additional online datasets generated by microarray platforms different from the one we investigated previously. We found that LINC00472 expression in breast cancer was regulated more possibly by promoter methylation than by the alteration of gene copy number. Analysis of additional datasets confirmed our previous findings of high expression of LINC00472 associated with ER-positive and low-grade tumors and favorable molecular subtypes. Finally, in nine datasets, we examined the association of LINC00472 expression with disease-free survival in patients with grade 2 tumors. Meta-analysis of the datasets showed that LINC00472 expression in breast tumors predicted the recurrence of breast cancer in patients with grade 2 tumors. In summary, our analyses confirm that LINC00472 is functionally a tumor suppressor, and that assessing its expression in breast tumors may have clinical implications in breast cancer management.

Keywords

Long non-coding RNA LINC00472 Breast Prognosis Grade 2 tumor Methylation 

Supplementary material

10549_2015_3632_MOESM1_ESM.docx (43 kb)
Supplementary material 1 (DOCX 42 kb)

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Yi Shen
    • 1
  • Zhanwei Wang
    • 1
  • Lenora WM Loo
    • 1
  • Yan Ni
    • 1
  • Wei Jia
    • 1
  • Peiwen Fei
    • 2
  • Harvey A. Risch
    • 3
  • Dionyssios Katsaros
    • 4
  • Herbert Yu
    • 1
  1. 1.Cancer Epidemiology ProgramUniversity of Hawaii Cancer CenterHonoluluUSA
  2. 2.Cancer Biology ProgramUniversity of Hawaii Cancer CenterHonoluluUSA
  3. 3.Department of Chronic Disease EpidemiologyYale School of Public HealthNew HavenUSA
  4. 4.Department of Surgical SciencesUniversity of TurinTurinItaly

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