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Breast Cancer Res Treat. 2015 Dec;154(3):473-82. doi: 10.1007/s10549-015-3632-8. Epub 2015 Nov 13.

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

Author information

1
Cancer Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA.
2
Cancer Biology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
3
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
4
Department of Surgical Sciences, University of Turin, Turin, Italy.
5
Cancer Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA. hyu@cc.hawaii.edu.

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:

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

PMID:
26564482
PMCID:
PMC4854534
DOI:
10.1007/s10549-015-3632-8
[Indexed for MEDLINE]
Free PMC Article

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