title: Epithelial-specific methylation marker: a potential plasma biomarker in advanced non-small cell lung cancer.
abstract: BACKGROUND
  Under physiological conditions, leukocytes contribute the majority of circulating DNA in plasma. Therefore, detection of methylation at the SHP-1 promoter 2 (SHP1P2) in plasma, which represents epithelial tumor-derived circulating nucleic acids, may serve as a potential noninvasive biomarker for non-small cell lung cancer (NSCLC).
  
  
  METHODS
  A quantitative polymerase chain reaction-based assay was used to determine the level of SHP1P2 methylation in plasma. Blood samples were prospectively collected from 58 patients with advanced NSCLC, 20 patients with early NSCLC, and 52 healthy volunteers.
  
  
  RESULTS
  Most of the healthy volunteers exhibited undetectable levels of SHP1P2 methylation. In contrast, the pretreatment levels of SHP1P2 methylation in the patients with NSCLC were readily detectable, with a median value of 770 pg ml(-1) (0-26,500 pg ml(-1)), which was significantly higher than that of the healthy controls. Furthermore, the patients with advanced NSCLC who presented baseline levels of SHP1P2 methylation of less than 700 pg ml(-1) exhibited enhanced median progression-free survival (5.2 versus 2.6 months, p = 0.009) and improved median overall survival (12.6 versus 7.6 months, p = 0.01) compared with patients who exhibited SHP1P2 methylation levels greater than 700 pg ml(-1). From a multivariate analysis, the levels of SHP1P2 methylation were significantly associated with survival rates in advanced NSCLC.
  
  
  CONCLUSIONS
  Measurement of the level of SHP1P2 methylation in plasma serves as a potential noninvasive biomarker for the prognostic assessment of patients with lung cancer. This biomarker can be used to develop risk-adaptive treatments for patients with lung cancer.
authors.affiliation: Inter-Department Program of Biomedical Sciences, Faculty of Graduate School, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Chanida
authors.initials: C
authors.lastname: Vinayanuwattikun
authors.forename: Virote
authors.initials: V
authors.lastname: Sriuranpong
authors.forename: Suebpong
authors.initials: S
authors.lastname: Tanasanvimon
authors.forename: Poonchavist
authors.initials: P
authors.lastname: Chantranuwat
authors.forename: Apiwat
authors.initials: A
authors.lastname: Mutirangura
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics*; D018287:Carcinoma, Large Cell / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D016022:Case-Control Studies; D004247:DNA / Q000097:blood / Q000235:genetics; D019175:DNA Methylation; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D004247:DNA; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6