title: SOX17 promoter methylation in plasma circulating tumor DNA of patients with non-small cell lung cancer.
abstract: BACKGROUND
  SOX17 belongs to the high-mobility group-box transcription factor superfamily and down-regulates the Wnt pathway. The aim of our study was to evaluate the prognostic significance of SOX17 promoter methylation in circulating tumor DNA (ctDNA) in plasma of non-small cell lung cancer (NSCLC) patients.
  
  
  METHODS
  We examined the methylation status of SOX17 promoter in 57 operable NSCLC primary tumors and paired adjacent non-cancerous tissues and in ctDNA isolated from 48 corresponding plasma samples as well as in plasma from 74 patients with advanced NSCLC and 49 healthy individuals. SOX17 promoter methylation was examined by Methylation Specific PCR (MSP).
  
  
  RESULTS
  In operable NSCLC, SOX17 promoter was fully methylated in primary tumors (57/57, 100%), and in corresponding ctDNA (27/48, 56.2%) while it was detected in only 1/49 (2.0%) healthy individuals. In advanced NSCLC, SOX17 promoter was methylated in ctDNA in 27/74 (36.4%) patients and OS was significantly different in favor of patients with non-methylated SOX17 promoter (p=0.012). Multivariate analysis revealed that SOX17 promoter methylation in ctDNA was an independent prognostic factor associated with OS in patients with advanced but not operable NSCLC.
  
  
  CONCLUSIONS
  Our results show that SOX17 promoter is highly methylated in primary tumors and in corresponding plasma samples both in operable and advanced NSCLC. In the advanced setting, SOX17 promoter methylation in plasma ctDNA has a statistical significant influence on NSCLC patient's survival time. Detection of SOX17 promoter methylation in plasma provides prognostic information and merits to be further evaluated as a circulating tumor biomarker in patients with operable and advanced NSCLC.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Balgkouranidou
authors.forename: Maria
authors.initials: M
authors.lastname: Chimonidou
authors.forename: Georgia
authors.initials: G
authors.lastname: Milaki
authors.forename: Emily
authors.initials: E
authors.lastname: Tsaroucha
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kakolyris
authors.forename: Vasilis
authors.initials: V
authors.lastname: Georgoulias
authors.forename: Evi
authors.initials: E
authors.lastname: Lianidou
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics*; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics*; D055760:SOXF Transcription Factors / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C109188:SOX17 protein, human; D055760:SOXF Transcription Factors