title: ACTN4 and the pathways associated with cell motility and adhesion contribute to the process of lung cancer metastasis to the brain.
abstract: BACKGROUND
  The aim of this study was to identify critical gene pathways that are associated with lung cancer metastasis to the brain.
  
  
  METHODS
  The RNA-Seq approach was used to establish the expression profiles of a primary lung cancer, adjacent benign tissue, and metastatic brain tumor from a single patient. The expression profiles of these three types of tissues were compared to define differentially expressed genes, followed by serial-cluster analysis, gene ontology analysis, pathway analysis, and knowledge-driven network analysis. Reverse transcription-polymerase chain reaction (RT-PCR) was used to validate the expression of essential candidate genes in tissues from ten additional patients.
  
  
  RESULTS
  Differential gene expression among these three types of tissues was classified into multiple clusters according to the patterns of their alterations. Further bioinformatic analysis of these expression profile data showed that the network of the signal transduction pathways related to actin cytoskeleton reorganization, cell migration, and adhesion was associated with lung cancer metastasis to the brain. The expression of ACTN4 (actinin, alpha 4), a cytoskeleton protein gene essential for cytoskeleton organization and cell motility, was significantly elevated in the metastatic brain tumor but not in the primary lung cancer tissue.
  
  
  CONCLUSIONS
  The signaling pathways involved in the regulation of cytoskeleton reorganization, cell motility, and focal adhesion play a role in the process of lung cancer metastasis to the brain. The contribution of ACTN4 to the process of lung cancer metastasis to the brain could be mainly through regulation of actin cytoskeleton reorganization, cell motility, and focal adhesion.
authors.affiliation: Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, 130033, China. gaoyufei1975@sina.cn.
authors.forename: Yufei
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, 130021, China. ghl1001@163.com.
authors.forename: Guanghu
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130024, China. sunlk@jlu.edu.cn.
authors.forename: Liankun
authors.initials: L
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, 130033, China. heyichun1989@sina.com.
authors.forename: Yichun
authors.initials: Y
authors.lastname: He
authors.affiliation: School of Stomatology, Jilin University, Changchun, 130021, China. lixiaoyan0510@163.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine Center, China-Japan Union Hospital, Jilin University, Changchun, 130033, China. 13514303555@163.com.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, 130024, China. 513837742@qq.com.
authors.forename: Jihan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Colorectal Surgery, China-Japan Union Hospital, Jilin University, Changchun, 130033, China. jy7555@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Laboratory Medicine Center, China-Japan Union Hospital, Jilin University, Changchun, 130033, China. shi123jingwei@163.com.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Shi
mesh_terms: D000185:Actinin / Q000096:biosynthesis / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D003599:Cytoskeleton / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015398:Signal Transduction / Q000235:genetics
chemical_list: C111453:ACTN4 protein, human; D000185:Actinin