title: DNA Methylation status of Wnt antagonist SFRP5 can predict the response to the EGFR-tyrosine kinase inhibitor therapy in non-small cell lung cancer.
abstract: BACKGROUND
  It is well known that genetic alternation of epidermal growth factor receptor (EGFR) plays critical roles in tumorgenesis of lung cancer and can predict outcome of non-small-cell lung cancer treatment, especially the EGFR tyrosine-kinase inhibitors (EGFR-TKIs) therapy. However, it is unclear whether epigenetic changes such as DNA methylation involve in the response to the EGFR-TKI therapy.
  
  
  METHODS
  Tumor samples from 155 patients with stages IIIB to IV NSCLC who received EGFR-TKI therapy were analyzed for DNA methylation status of Wnt antagonist genes, including SFRP1, SFRP2, SFRP5, DKK3, WIF1, and APC, using methylation specific PCR (MSP) method. EGFR mutations detections were performed in the same tissues samples using Denaturing High Performance Liquid Chromatography (DHPLC).
  
  
  RESULTS
  We found that Wnt antagonists tend to methylate simultaneously. Methylation of sFRP1 and sFRP5 are reversely correlated with EGFR mutation (P = 0.005, P = 0.011). However, no correlations of methylations of other Wnt antagonist genes with EGFR mutation were found. The patients with methylated SFRP5 have a significant shorter progression free survival than those with unmethylated SFRP5 in response to EGFR-TKI treatment (P = 0.002), which is independent of EGFR genotype.
  
  
  CONCLUSIONS
  Patients with unmethylated SFRP5 are more likely to benefit from EGFR-TKI therapy.
authors.affiliation: Department of Thoracic Medical Oncology Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.forename: Yuyan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jianchun
authors.initials: J
authors.lastname: Duan
authors.forename: Hua
authors.initials: H
authors.lastname: Bai
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Wang
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.forename: Minglei
authors.initials: M
authors.lastname: Zhuo
authors.forename: Shuhang
authors.initials: S
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.forename: Tongtong
authors.initials: T
authors.lastname: An
authors.forename: Meina
authors.initials: M
authors.lastname: Wu
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D054316:Biomarkers, Pharmacological; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D019175:DNA Methylation / Q000235:genetics*; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome; D060449:Wnt Signaling Pathway; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D054316:Biomarkers, Pharmacological; D066246:ErbB Receptors; D005136:Eye Proteins; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; C118511:SFRP5 protein, human; D000094742:Secreted Frizzled-Related Proteins