title: Identification of Novel Breast Cancer Subtype-Specific Biomarkers by Integrating Genomics Analysis of DNA Copy Number Aberrations and miRNA-mRNA Dual Expression Profiling.
abstract: Breast cancer is a heterogeneous disease with well-defined molecular subtypes. Currently, comparative genomic hybridization arrays (aCGH) techniques have been developed rapidly, and recent evidences in studies of breast cancer suggest that tumors within gene expression subtypes share similar DNA copy number aberrations (CNA) which can be used to further subdivide subtypes. Moreover, subtype-specific miRNA expression profiles are also proposed as novel signatures for breast cancer classification. The identification of mRNA or miRNA expression-based breast cancer subtypes is considered an instructive means of prognosis. Here, we conducted an integrated analysis based on copy number aberrations data and miRNA-mRNA dual expression profiling data to identify breast cancer subtype-specific biomarkers. Interestingly, we found a group of genes residing in subtype-specific CNA regions that also display the corresponding changes in mRNAs levels and their target miRNAs' expression. Among them, the predicted direct correlation of BRCA1-miR-143-miR-145 pairs was selected for experimental validation. The study results indicated that BRCA1 positively regulates miR-143-miR-145 expression and miR-143-miR-145 can serve as promising novel biomarkers for breast cancer subtyping. In our integrated genomics analysis and experimental validation, a new frame to predict candidate biomarkers of breast cancer subtype is provided and offers assistance in order to understand the potential disease etiology of the breast cancer subtypes.
authors.affiliation: Institute of Biomedical Engineering, Capital Medical University, Beijing 100069, China.
authors.forename: Dongguo
authors.identifier: 0000-0001-6327-8315
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Biomedical Engineering, Capital Medical University, Beijing 100069, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xia
authors.affiliation: Institute of Basic Medical Science, Peking Union Medical College, Qinghua University, No. 5 Dong Dan San Tiao, Beijing 100005, China.
authors.forename: Zhen-ya
authors.initials: ZY
authors.lastname: Li
authors.affiliation: Institute of Biomedical Engineering, Capital Medical University, Beijing 100069, China.
authors.forename: Lin
authors.identifier: 0000-0001-6309-3572
authors.initials: L
authors.lastname: Hua
authors.affiliation: Institute of Biomedical Engineering, Capital Medical University, Beijing 100069, China.
authors.forename: Lin
authors.identifier: 0000-0002-9190-5475
authors.initials: L
authors.lastname: Li
mesh_terms: D019313:BRCA1 Protein / Q000096:biosynthesis* / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D053858:Metabolic Networks and Pathways / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; D014408:Biomarkers, Tumor; C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger