title: Identification of Epstein-Barr virus-induced gene 3 as a novel serum and tissue biomarker and a therapeutic target for lung cancer.
abstract: OBJECTIVE
  This study aims to identify novel biomarkers and therapeutic targets for lung cancer.
  
  
  METHODS
  We carried out gene expression profile analysis of 120 lung cancers to screen for genes encoding transmembrane/secretory molecules that are commonly transactivated in lung cancers. Epstein-Barr virus-induced gene 3 (EBI3), which encodes a secretory glycoprotein, was selected as a good candidate. Immunohistochemical staining using tissue microarray consisting of 414 non-small cell lung cancers was applied to examine the expression level and prognostic value of EBI3. Serum EBI3 levels in 400 individuals for training assays (274 lung cancers and 126 healthy volunteers) and those in 173 individuals for validation analysis (132 lung cancers and 41 healthy volunteers) were measured by ELISA. The role of EBI3 in cancer cell growth was examined by siRNA and cell growth assays, using cells stably expressing exogenous EBI3.
  
  
  RESULTS
  Immunohistochemical staining of EBI3 using tissue microarrays revealed that a high level of EBI3 expression was associated with a poor prognosis of lung cancer (P = 0.0014) and multivariate analysis confirmed it to be an independent prognostic factor (P = 0.0439). Serum levels of EBI3 in the training set were found to be significantly higher in lung cancer patients than in healthy volunteers; this result was also observed in the validation set. Furthermore, reduction in EBI3 expression by siRNA suppressed cancer cell proliferation whereas induction of exogenous EBI3 conferred growth-promoting activity.
  
  
  CONCLUSIONS
  EBI3 is a potential serum and tissue biomarker as well as therapeutic target for lung cancer.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Nishino
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takano
authors.forename: Hideto
authors.initials: H
authors.lastname: Oshita
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Ishikawa
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ito
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Nakayama
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Eiju
authors.initials: E
authors.lastname: Tsuchiya
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007378:Interleukins / Q000097:blood / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D015778:Minor Histocompatibility Antigens; D058990:Molecular Targeted Therapy; D011379:Prognosis; D046888:Tissue Array Analysis; D015533:Transcriptional Activation
chemical_list: D014408:Biomarkers, Tumor; C097732:EBI3 protein, human; D007378:Interleukins; D015778:Minor Histocompatibility Antigens