title: The impact of non-tumor-derived circulating nucleic acids implicates the prognosis of non-small cell lung cancer.
abstract: BACKGROUND
  A high level of circulating DNA (cirDNA) in cancer patients has been correlated with poor outcomes. Studies have demonstrated the critical contributions of the tumor-derived cirDNA. In this report, we investigated the roles of the non-tumor-derived cirDNA (nt-cirDNA) in determining the prognosis of non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Plasma samples from 58 advanced NSCLC patients and 52 controls were collected. The nt-cirDNA levels were assessed with qPCR assay to detect the unmethylation status of an epithelial-specific marker, the SHP-1 promoter 2 (unmethylated SHP1P2). Clinicopathological correlations were analyzed.
  
  
  RESULTS
  There was a significant increase in the total amount of cirDNA in NSCLC patients compared with controls: 4.3 ng ml(-1) [0.82-49.8] and 2.0 ng ml(-1) [0.03-26.9], respectively (p < 0.01). An increased amount of the unmethylated SHP1P2 in advanced NSCLC was also detected: 3.4 ng ml(-1) [1.2-24.8] versus 2.0 ng ml(-1) [0.03-26.9] in the controls (p = 0.026). Survival analyses revealed that high levels of total cirDNA and unmethylated SHP1P2 were significantly associated with decreased survival. However, the total cirDNA had a better prognostic correlation than the unmethylated SHP1P2. Multivariate analysis identified total cirDNA (p = 0.004) and systemic treatment (p = 0.002) as independent prognostic parameters.
  
  
  CONCLUSIONS
  The level of total cirDNA in NSCLC is an important prognostic parameter that demonstrates the contributions from both tumor-derived sources and non-tumor-derived sources.
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: Pakorn
authors.initials: P
authors.lastname: Winayanuwattikun
authors.forename: Poonchavist
authors.initials: P
authors.lastname: Chantranuwat
authors.forename: Apiwat
authors.initials: A
authors.lastname: Mutirangura
authors.forename: Virote
authors.initials: V
authors.lastname: Sriuranpong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000401:mortality; D016022:Case-Control Studies; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009696:Nucleic Acids / Q000097:blood*; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D011379:Prognosis; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000097:blood* / Q000235:genetics; D012907:Smoking / Q000009:adverse effects; D016019:Survival Analysis
chemical_list: D004273:DNA, Neoplasm; D009696:Nucleic Acids; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6