title: Synchronous alterations of Wnt and epidermal growth factor receptor signaling pathways through aberrant methylation and mutation in non small cell lung cancer.
abstract: OBJECTIVE
  The Wnt and epidermal growth factor receptor (EGFR) signaling pathways play crucial roles in the pathogenesis of a variety of malignant tumors. Although the details of each cascade are understood, very little is known about their collective effects in non-small cell lung cancer (NSCLC).
  
  
  METHODS
  A total of 238 NSCLC samples were examined for methylation of Wnt antagonists [secreted frizzled-related protein (sFRP)-1, sFRP-2, sFRP-5, Wnt inhibitory factor-1, and Dickkopf-3] and for EGFR and KRAS mutations. Protein expression levels of beta-catenin were assayed in 91 of the 238 NSCLCs.
  
  
  RESULTS
  We found that (a) aberrant methylation of Wnt antagonists is common in NSCLCs; (b) methylation of sFRP-2 is more prevalent in females, nonsmokers, and adenocarcinoma cases; (c) Dickkopf-3 methylation is significantly associated with a poor prognosis in adenocarcinomas; (d) there is a positive correlation between activated EGFR mutation and nuclear accumulation of beta-catenin; (e) KRAS mutation and aberrant methylation of Wnt antagonists are positively correlated; and (f) EGFR mutation is significantly associated with a good prognosis in tumors lacking methylated Wnt antagonist genes.
  
  
  CONCLUSIONS
  These results contribute to a better understanding of the cross-talk between the Wnt and EGFR signaling pathways and help foster development of chemotherapeutic treatments in NSCLCs.
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. smakoto528@yahoo.co.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Shigematsu
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakajima
authors.forename: Rieko
authors.initials: R
authors.lastname: Kubo
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Motohashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sekine
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Shibuya
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Iizasa
authors.forename: Kenzo
authors.initials: K
authors.lastname: Hiroshima
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Adi F
authors.initials: AF
authors.lastname: Gazdar
authors.forename: Takehiko
authors.initials: T
authors.lastname: Fujisawa
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051153:Wnt Proteins; D066246:ErbB Receptors