title: Genes dysregulated to different extent or oppositely in estrogen receptor-positive and estrogen receptor-negative breast cancers.
abstract: BACKGROUND
  Directly comparing gene expression profiles of estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancers cannot determine whether differentially expressed genes between these two subtypes result from dysregulated expression in ER+ cancer or ER- cancer versus normal controls, and thus would miss critical information for elucidating the transcriptomic difference between the two subtypes.
  
  
  RESULTS
  Using microarray datasets from TCGA, we classified the genes dysregulated in both ER+ and ER- cancers versus normal controls into two classes: (i) genes dysregulated in the same direction but to a different extent, and (ii) genes dysregulated to opposite directions, and then validated the two classes in RNA-sequencing datasets of independent cohorts. We showed that the genes dysregulated to a larger extent in ER+ cancers than in ER- cancers enriched in glycerophospholipid and polysaccharide metabolic processes, while the genes dysregulated to a larger extent in ER- cancers than in ER+ cancers enriched in cell proliferation. Phosphorylase kinase and enzymes of glycosylphosphatidylinositol (GPI) anchor biosynthesis were upregulated to a larger extent in ER+ cancers than in ER- cancers, whereas glycogen synthase and phospholipase A2 were downregulated to a larger extent in ER+ cancers than in ER- cancers. We also found that the genes oppositely dysregulated in the two subtypes significantly enriched with known cancer genes and tended to closely collaborate with the cancer genes. Furthermore, we showed the possibility that these oppositely dysregulated genes could contribute to carcinogenesis of ER+ and ER- cancers through rewiring different subpathways.
  
  
  CONCLUSIONS
  GPI-anchor biosynthesis and glycogenolysis were elevated and hydrolysis of phospholipids was depleted to a larger extent in ER+ cancers than in ER- cancers. Our findings indicate that the genes oppositely dysregulated in the two subtypes are potential cancer genes which could contribute to carcinogenesis of both ER+ and ER- cancers through rewiring different subpathways.
authors.affiliation: Bioinformatics Centre and Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: Xianxiao
authors.initials: X
authors.lastname: Zhou
authors.forename: Tongwei
authors.initials: T
authors.lastname: Shi
authors.forename: Bailiang
authors.initials: B
authors.lastname: Li
authors.forename: Yuannv
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiaopei
authors.initials: X
authors.lastname: Shen
authors.forename: Hongdong
authors.initials: H
authors.lastname: Li
authors.forename: Guini
authors.initials: G
authors.lastname: Hong
authors.forename: Chunyang
authors.initials: C
authors.lastname: Liu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Guo
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D046228:Microarray Analysis; D060066:Protein Interaction Maps; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA
chemical_list: D011960:Receptors, Estrogen