title: Molecular portraits revealing the heterogeneity of breast tumor subtypes defined using immunohistochemistry markers.
abstract: Breast cancer is highly heterogeneous. The subtypes defined using immunohistochemistry markers and gene expression profilings (GEP) are related but not equivalent, with inter-connections under investigated. Our previous study revealed a set of differentially expressed genes (diff-genes), containing 1015 mRNAs and 69 miRNAs, which characterize the immunohistochemistry-defined breast tumor subtypes at the GEP level. However, they may convey redundant information due to the large amount of genes included. By reducing the dimension of the diff-genes, we identified 119 mRNAs and 20 miRNAs best explaining breast tumor heterogeneity with the most succinct number of genes found using hierarchical clustering and nearest-to-center principle. The final signature panel contains 119 mRNAs, whose superiority over diff-genes was replicated in two independent public datasets. The comparison of our signature with two pioneering signatures, the Sorlie's signature and PAM50, suggests a novel marker, FOXA1, in breast cancer classification. Subtype-specific feature genes are reported to characterize each immunohistochemistry-defined subgroup. Pathway and network analysis reveal the critical roles of Notch signalings in [ER+|PR+]HER2- and cell cycle in [ER+|PR+]HER2+ tumors. Our study reveals the primary differences among the four immunohistochemistry-defined breast tumors at the mRNA and miRNA levels, and proposes a novel signature for breast tumor subtyping given GEP data.
authors.affiliation: School of Biotechnology, Jiangnan University, Wuxi 214122, China.|National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Dai
authors.affiliation: School of Science, Jiangnan University, Wuxi 214122, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Biotechnology, Jiangnan University, Wuxi 214122, China.|National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Zhonghu
authors.initials: Z
authors.lastname: Bai
authors.affiliation: School of Science, Jiangnan University, Wuxi 214122, China.
authors.forename: Xu-Qing
authors.initials: XQ
authors.lastname: Tang
mesh_terms: D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D015203:Reproducibility of Results; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012333:RNA, Messenger