title: Methylation markers of early-stage non-small cell lung cancer.
abstract: BACKGROUND
  Despite of intense research in early cancer detection, there is a lack of biomarkers for the reliable detection of malignant tumors, including non-small cell lung cancer (NSCLC). DNA methylation changes are common and relatively stable in various types of cancers, and may be used as diagnostic or prognostic biomarkers.
  
  
  METHODS
  We performed DNA methylation profiling of samples from 48 patients with stage I NSCLC and 18 matching cancer-free lung samples using microarrays that cover the promoter regions of more than 14,500 genes. We correlated DNA methylation changes with gene expression levels and performed survival analysis.
  
  
  RESULTS
  We observed hypermethylation of 496 CpGs in 379 genes and hypomethylation of 373 CpGs in 335 genes in NSCLC. Compared to adenocarcinoma samples, squamous cell carcinoma samples had 263 CpGs in 223 hypermethylated genes and 513 CpGs in 436 hypomethylated genes. 378 of 869 (43.5%) CpG sites discriminating the NSCLC and control samples showed an inverse correlation between CpG site methylation and gene expression levels. As a result of a survival analysis, we found 10 CpGs in 10 genes, in which the methylation level differs in different survival groups.
  
  
  CONCLUSIONS
  We have identified a set of genes with altered methylation in NSCLC and found that a minority of them showed an inverse correlation with gene expression levels. We also found a set of genes that associated with the survival of the patients. These newly-identified marker candidates for the molecular screening of NSCLC will need further analysis in order to determine their clinical utility.
authors: Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors: Kaie
authors: K
authors: Lokk
authors: Tõnu
authors: T
authors: Vooder
authors: Raivo
authors: R
authors: Kolde
authors: Kristjan
authors: K
authors: Välk
authors: Urmo
authors: U
authors: Võsa
authors: Retlav
authors: R
authors: Roosipuu
authors: Lili
authors: L
authors: Milani
authors: Krista
authors: K
authors: Fischer
authors: Marina
authors: M
authors: Koltsina
authors: Egon
authors: E
authors: Urgard
authors: Tarmo
authors: T
authors: Annilo
authors: Andres
authors: A
authors: Metspalu
authors: Neeme
authors: N
authors: Tõnisson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001519:Behavior; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000235:genetics; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor