title: Topological network analysis of differentially expressed genes in cancer cells with acquired gefitinib resistance.
abstract: OBJECTIVE
  Despite great effort to elucidate the process of acquired gefitinib resistance (AGR) in order to develop successful chemotherapy, the precise mechanisms and genetic factors of such resistance have yet to be elucidated.
  
  
  METHODS
  We performed a cross-platform meta-analysis of three publically available microarray datasets related to cancer with AGR. For the top 100 differentially expressed genes (DEGs), we clustered functional modules of hub genes in a gene co-expression network and a protein-protein interaction network. We conducted a weighted correlation network analysis of total DEGs in microarray dataset GSE 34228. The identified DEGs were functionally enriched by Gene Ontology (GO) function and KEGG pathway.
  
  
  RESULTS
  We identified a total of 1,033 DEGs (510 up-regulated, 523 down-regulated, and 109 novel genes). Among the top 100 up- or down-regulated DEGs, many genes were found in different types of cancers and tumors. Through integrative analysis of two systemic networks, we selected six hub DEGs (Pre-B-cell leukemia homeobox1, Transient receptor potential cation channel subfamily C member 1, AXL receptor tyrosine kinase, S100 calcium binding protein A9, S100 calcium binding protein A8, and Nucleotide-binding oligomerization domain containing 2) associated with calcium homeostasis and signaling, apoptosis, transcriptional regulation, or chemoresistance. We confirmed a correlation of expression of these genes in the microarray dataset.
  
  
  CONCLUSIONS
  Our study may lead to comprehensive insights into the complex mechanism of AGR and to novel gene expression signatures useful for further clinical studies.
authors.affiliation: Department of Biochemistry, School of Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Young Seok
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Plant Genomics Laboratory, Department of Applied Plant Science, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Sun Goo
authors.initials: SG
authors.lastname: Hwang
authors.affiliation: Department of Biochemistry, School of Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Jin Ki
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Plastic and Reconstructive Surgery, College of Medicine, Yonsei University, Seoul, Republic of Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Park
authors.affiliation: Department of Biochemistry, School of Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Young Rae
authors.initials: YR
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, School of Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Myeong
authors.affiliation: School of Korean Medicine, Pusan National University, Yangsan, Republic of Korea.
authors.forename: Kang
authors.initials: K
authors.lastname: Kwon
authors.affiliation: Plant Genomics Laboratory, Department of Applied Plant Science, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Cheol Seong
authors.initials: CS
authors.lastname: Jang
authors.affiliation: Department of Biochemistry, School of Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Noh
authors.affiliation: Department of Biochemistry, School of Medicine, Konkuk University, Seoul, Republic of Korea.
authors.forename: Sung Young
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D019295:Computational Biology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D000077156:Gefitinib; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D058977:Molecular Sequence Annotation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000077156:Gefitinib
keywords: DEGs; Meta-analysis; acquired drug resistance; differentially expressed genes; gefitinib; microarray