title: Methylation profiling in non-small cell lung cancer: clinical implications.
abstract: The aim of this study was to identify a panel of methylation markers that             distinguish non-small cell lung cancers (NSCLCs) from normal lung tissues. We             also studied the relation of the methylation profile to clinicopathological factors             in NSCLC. We collected a series of 46 NSCLC samples and their corresponding control             tissues and analyzed them to determine gene methylation status using the Illumina             GoldenGate Methylation bead array, which screens up to 1505 CpG sites from 803             different genes. We found that 120 CpG sites, corresponding to 88 genes were hypermethylated             in tumor samples and only 17 CpG sites (16 genes) were hypomethylated when compared             with controls. Clustering analysis of these 104 genes discriminates almost perfectly             between tumors and normal samples. Global hypermethylation was significantly associated             with a worse prognosis in stage IIIA NSCLC patients (P=0.012). Moreover, hypermethylation             of the CALCA and MMP-2 genes were statistically associated to a poor clinical             evolution of patients, independently of TNM tumor stage (P=0.06, RR=2.64; P=0.04,             RR=2.96, respectively). However, hypermethylation of RASSF1 turned out to be a             protective variable (P=0.02; RR=0.53). In conclusion, our results could be useful             for establishing a gene methylation pattern for the detection and prognosis of             NSCLC.
authors.affiliation: Department of Biochemistry and Molecular Biology, Complutense University, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Morán
authors.forename: Tamara
authors.initials: T
authors.lastname: Fernández-Marcelo
authors.forename: Juan
authors.initials: J
authors.lastname: Carro
authors.forename: Carmen
authors.initials: C
authors.lastname: De Juan
authors.forename: Irene
authors.initials: I
authors.lastname: Pascua
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Head
authors.forename: Ana
authors.initials: A
authors.lastname: Gómez
authors.forename: Florentino
authors.initials: F
authors.lastname: Hernando
authors.forename: Antonio-José
authors.initials: AJ
authors.lastname: Torres
authors.forename: Manuel
authors.initials: M
authors.lastname: Benito
authors.forename: Pilar
authors.initials: P
authors.lastname: Iniesta
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011379:Prognosis