title: Molecular Features of Triple Negative Breast Cancer: Microarray Evidence and Further Integrated Analysis.
abstract: OBJECTIVE
  Breast cancer is a heterogeneous disease usually including four molecular subtypes such as luminal A, luminal B, HER2-enriched, and triple-negative breast cancer (TNBC). TNBC is more aggressive than other breast cancer subtypes. Despite major advances in ER-positive or HER2-amplified breast cancer, there is no targeted agent currently available for TNBC, so it is urgent to identify new potential therapeutic targets for TNBC.
  
  
  METHODS
  We first used microarray analysis to compare gene expression profiling between TNBC and non-TNBC. Furthermore an integrated analysis was conducted based on our own and published data, leading to more robust, reproducible and accurate predictions. Additionally, we performed qRT-PCR in breast cancer cell lines to verify the findings in integrated analysis.
  
  
  RESULTS
  After searching Gene Expression Omnibus database (GEO), two microarray studies were obtained according to the inclusion criteria. The integrated analysis was conducted, including 30 samples of TNBC and 77 samples of non-TNBC. 556 genes were found to be consistently differentially expressed (344 up-regulated genes and 212 down-regulated genes in TNBC). Functional annotation for these differentially expressed genes (DEGs) showed that the most significantly enriched Gene Ontology (GO) term for molecular functions was protein binding (GO: 0005515, P = 6.09E-21), while that for biological processes was signal transduction (GO: 0007165, P = 9.46E-08), and that for cellular component was cytoplasm (GO: 0005737, P = 2.09E-21). The most significant pathway was Pathways in cancer (P = 6.54E-05) based on Kyoto Encyclopedia of Genes and Genomes (KEGG). DUSP1 (Degree = 21), MYEOV2 (Degree = 15) and UQCRQ (Degree = 14) were identified as the significant hub proteins in the protein-protein interaction (PPI) network. Five genes were selected to perform qRT-PCR in seven breast cancer cell lines, and qRT-PCR results showed that the expression pattern of selected genes in TNBC lines and non-TNBC lines was nearly consistent with that in the integrated analysis.
  
  
  CONCLUSIONS
  This study may help to understand the pathogenesis of different breast cancer subtypes, contributing to the successful identification of therapeutic targets for TNBC.
authors.affiliation: Department of Breast Surgery, The first affiliated hospital of Shenzhen university, the Second People's Hospital of Shenzhen, Shenzhen 518035, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Laboratory Medicine and Pathology, Masonic Cancer Center, University of Minnesota, UMN Twin Cities, Minneapolis 55455, Minnesota, United States of America.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Breast Surgery, The first affiliated hospital of Shenzhen university, the Second People's Hospital of Shenzhen, Shenzhen 518035, China.
authors.forename: Weicai
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Breast Surgery, The first affiliated hospital of Shenzhen university, the Second People's Hospital of Shenzhen, Shenzhen 518035, China.
authors.forename: Huisheng
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Breast Surgery, The first affiliated hospital of Shenzhen university, the Second People's Hospital of Shenzhen, Shenzhen 518035, China.
authors.forename: Zishan
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Breast Surgery, The first affiliated hospital of Shenzhen university, the Second People's Hospital of Shenzhen, Shenzhen 518035, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, The first affiliated hospital of Shenzhen university, the Second People's Hospital of Shenzhen, Shenzhen 518035, China.
authors.forename: Guojin
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Breast Surgery, The first affiliated hospital of Shenzhen university, the Second People's Hospital of Shenzhen, Shenzhen 518035, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Breast Surgery, The first affiliated hospital of Shenzhen university, the Second People's Hospital of Shenzhen, Shenzhen 518035, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Yu
mesh_terms: D000328:Adult; D006801:Humans; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics*