title: LINC00472 expression is regulated by promoter methylation and associated with disease-free survival in patients with grade 2 breast cancer.
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.
authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA.
authors.forename: Zhanwei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA.
authors.forename: Lenora W M
authors.initials: LW
authors.lastname: Loo
authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Cancer Biology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
authors.forename: Peiwen
authors.initials: P
authors.lastname: Fei
authors.affiliation: Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Risch
authors.affiliation: Department of Surgical Sciences, University of Turin, Turin, Italy.
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA. hyu@cc.hawaii.edu.
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D019175:DNA Methylation; D030541:Databases, Genetic; D018572:Disease-Free Survival; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: C000604777:LINC00472 RNA, human; D062085:RNA, Long Noncoding
keywords: Breast; Grade 2 tumor; LINC00472; Long non-coding RNA; Methylation; Prognosis