title: Association of large noncoding RNA HOTAIR expression and its downstream intergenic CpG island methylation with survival in breast cancer.
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.
authors.affiliation: Department of Chronic Disease Epidemiology, Yale Cancer Center, Yale School of Public Health, 60 College Street, New Haven, CT 06520-8034, USA. lingeng.lu@yale.edu
authors.forename: Lingeng
authors.initials: L
authors.lastname: Lu
authors.forename: Guangjian
authors.initials: G
authors.lastname: Zhu
authors.forename: Chong
authors.initials: C
authors.lastname: Zhang
authors.forename: Qian
authors.initials: Q
authors.lastname: Deng
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.forename: Susan T
authors.initials: ST
authors.lastname: Mayne
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
authors.forename: Lina
authors.initials: L
authors.lastname: Mu
authors.forename: Emilie Marion
authors.initials: EM
authors.lastname: Canuto
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gregori
authors.forename: Chiara
authors.initials: C
authors.lastname: Benedetto
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D062085:RNA, Long Noncoding / Q000235:genetics*; D013002:Somatomedins / Q000235:genetics; D055815:Young Adult
chemical_list: C561566:HOTAIR long untranslated RNA, human; D062085:RNA, Long Noncoding; D013002:Somatomedins