title: CFL1 expression levels as a prognostic and drug resistance marker in nonsmall cell lung cancer.
abstract: BACKGROUND
  Nonsmall cell lung cancer (NSCLC) is the major determinant of overall cancer mortality worldwide. Despite progress in molecular research, current treatments offer limited benefits. Because NSCLC generates early metastasis, and this behavior requires great cell motility, herein the authors assessed the potential value of CFL1 gene (main member of the invasion/metastasis pathway) as a prognostic and predictive NSCLC biomarker.
  
  
  METHODS
  Metadata analysis of tumor tissue microarray was applied to examine expression of CFL1 in archival lung cancer samples from 111 patients, and its clinicopathologic significance was investigated. The robustness of the finding was validated using another independent data set. Finally, the authors assayed in vitro the role of CFL1 levels in tumor invasiveness and drug resistance using 6 human NSCLC cell lines with different basal degrees of CFL1 gene expression.
  
  
  RESULTS
  CFL1 levels in biopsies discriminate between good and bad prognosis at early tumor stages (IA, IB, and IIA/B), where high CFL1 levels are correlated with lower overall survival rate (P<.0001). Biomarker performance was further analyzed by immunohistochemistry, hazard ratio (P<.001), and receiver-operating characteristic curve (area=0.787; P<.001). High CFL1 mRNA levels and protein content are positively correlated with cellular invasiveness (determined by Matrigel Invasion Chamber System) and resistance (2-fold increase in drug 50% growth inhibition dose) against a list of 22 alkylating agents. Hierarchical clustering analysis of the CFL1 gene network had the same robustness for stratified NSCLC patients.
  
  
  CONCLUSIONS
  This study indicates that the CFL1 gene and its functional gene network can be used as prognostic biomarkers for NSCLC and could also guide chemotherapeutic interventions.
authors.affiliation: Department of Biochemistry, ICBS/Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Mauro Antonio Alves
authors.initials: MA
authors.lastname: Castro
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.forename: Stephanie
authors.initials: S
authors.lastname: Zdanov
authors.forename: Marcio
authors.initials: M
authors.lastname: Soares
authors.forename: Carolina Beatriz
authors.initials: CB
authors.lastname: Müller
authors.forename: Fernanda Martins
authors.initials: FM
authors.lastname: Lopes
authors.forename: Alfeu
authors.initials: A
authors.lastname: Zanotto-Filho
authors.forename: Marilda
authors.initials: M
authors.lastname: da Cruz Fernandes
authors.forename: Jose Claudio Fonseca
authors.initials: JC
authors.lastname: Moreira
authors.forename: Emily
authors.initials: E
authors.lastname: Shacter
authors.forename: Fábio
authors.initials: F
authors.lastname: Klamt
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality; D045744:Cell Line, Tumor; D051338:Cofilin 1 / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D051338:Cofilin 1