title: A pathway-based classification of breast cancer integrating data on differentially expressed genes, copy number variations and microRNA target genes.
abstract: Breast cancer is a clinically heterogeneous disease characterized by distinct molecular aberrations. Understanding the heterogeneity and identifying subgroups of breast cancer are essential to improving diagnoses and predicting therapeutic responses. In this paper, we propose a classification scheme for breast cancer which integrates data on differentially expressed genes (DEGs), copy number variations (CNVs) and microRNAs (miRNAs)-regulated mRNAs. Pathway information based on the estimation of molecular pathway activity is also applied as a postprocessor to optimize the classifier. A total of 250 malignant breast tumors were analyzed by k-means clustering based on the patterns of the expression profiles of 215 intrinsic genes, and the classification performances were compared with existing breast cancer classifiers including the BluePrint and the 625-gene classifier. We show that a classification scheme which incorporates pathway information with various genetic variations achieves better performance than classifiers based on the expression levels of individual genes, and propose that the identified signature serves as a basic tool for identifying rational therapeutic opportunities for breast cancer patients.
authors.affiliation: Bio&Health Team, Future IT R&D Laboratory, LGE Advanced Research Institute, Seoul 137-724, Korea.
authors.forename: Hae-Seok
authors.initials: HS
authors.lastname: Eo
authors.forename: Jee Yeon
authors.initials: JY
authors.lastname: Heo
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Choi
authors.forename: Youngdon
authors.initials: Y
authors.lastname: Hwang
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Choi
mesh_terms: D001943:Breast Neoplasms / Q000145:classification* / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D035683:MicroRNAs