PURPOSE: Global hypomethylation and the hypermethylation of gene promoter regions are common events in tumor DNA. The aim of this study was to evaluate the prognostic significance of both global hypomethylation and gene promoter hypermethylation in DNA from non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Genomic DNA was obtained from the tumor tissue of 379 NSCLC patients who underwent surgery. Methylation levels were measured by real-time PCR following bisulfite modification of DNA and were correlated with clinicopathologic parameters and patient prognosis. Methylation of long interspersed nuclear element 1 (LINE-1) was used as a surrogate marker for global methylation. Hypermethylation of the APC, CDH13, and RASSF1 promoter regions was also evaluated. RESULTS: Tumor tissue showed significantly higher CDH13 and RASSF1 methylation levels compared with normal lung tissue, but lower LINE-1 methylation levels. APC, RASSF1, and LINE-1 methylation levels were significant prognostic factors in univariate analysis of an initial cohort of 234 cases. APC and LINE-1 methylation remained significant prognostic factors in multivariate analysis that included age, gender, smoking history, histologic type, and pathologic stage. LINE-1 methylation showed marginally significant prognostic value in stage IA and IB disease. Expansion of the study cohort to 364 cases revealed that LINE-1 methylation had significant prognostic value for stage IA NSCLC patients in multivariate analysis. CONCLUSIONS: LINE-1 hypomethylation was an independent marker of poor prognosis in stage IA NSCLC. Validation of this finding in additional tumor cohorts could have clinical relevance for the management of early-stage NSCLC.
PURPOSE: Global hypomethylation and the hypermethylation of gene promoter regions are common events in tumor DNA. The aim of this study was to evaluate the prognostic significance of both global hypomethylation and gene promoter hypermethylation in DNA from non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Genomic DNA was obtained from the tumor tissue of 379 NSCLCpatients who underwent surgery. Methylation levels were measured by real-time PCR following bisulfite modification of DNA and were correlated with clinicopathologic parameters and patient prognosis. Methylation of long interspersed nuclear element 1 (LINE-1) was used as a surrogate marker for global methylation. Hypermethylation of the APC, CDH13, and RASSF1 promoter regions was also evaluated. RESULTS:Tumor tissue showed significantly higher CDH13 and RASSF1 methylation levels compared with normal lung tissue, but lower LINE-1 methylation levels. APC, RASSF1, and LINE-1 methylation levels were significant prognostic factors in univariate analysis of an initial cohort of 234 cases. APC and LINE-1 methylation remained significant prognostic factors in multivariate analysis that included age, gender, smoking history, histologic type, and pathologic stage. LINE-1 methylation showed marginally significant prognostic value in stage IA and IB disease. Expansion of the study cohort to 364 cases revealed that LINE-1 methylation had significant prognostic value for stage IA NSCLCpatients in multivariate analysis. CONCLUSIONS: LINE-1 hypomethylation was an independent marker of poor prognosis in stage IA NSCLC. Validation of this finding in additional tumor cohorts could have clinical relevance for the management of early-stage NSCLC.
Authors: Milica Kontic; Jelena Stojsic; Dragana Jovanovic; Vera Bunjevacki; Simona Ognjanovic; Jacquelyn Kuriger; Susan Puumala; Heather H Nelson Journal: Clin Lung Cancer Date: 2011-12-13 Impact factor: 4.785
Authors: Arif Akbar Bhat; Hilal Ahmad Wani; Ajaz Ahmad Waza; Rawoof Ahmad Malik; Akbar Masood; Showkat Jeelani; Showkat Kadla; Sabhiya Majid Journal: J Gastrointest Oncol Date: 2016-12
Authors: Sara Prior; Isabelle R Miousse; Etienne Nzabarushimana; Rupak Pathak; Charles Skinner; Kristy R Kutanzi; Antiño R Allen; Jacob Raber; Alan J Tackett; Martin Hauer-Jensen; Gregory A Nelson; Igor Koturbash Journal: Environ Res Date: 2016-07-14 Impact factor: 6.498
Authors: Jonah B Sacha; In-Jeong Kim; Lianchun Chen; Jakir H Ullah; David A Goodwin; Heather A Simmons; Daniel I Schenkman; Frederike von Pelchrzim; Robert J Gifford; Francesca A Nimityongskul; Laura P Newman; Samantha Wildeboer; Patrick B Lappin; Daisy Hammond; Philip Castrovinci; Shari M Piaskowski; Jason S Reed; Kerry A Beheler; Tharsika Tharmanathan; Ningli Zhang; Sophie Muscat-King; Melanie Rieger; Carla Fernandes; Klaus Rumpel; Joseph P Gardner; Douglas H Gebhard; Juliann Janies; Ahmed Shoieb; Brian G Pierce; Dusko Trajkovic; Eva Rakasz; Sing Rong; Michael McCluskie; Clare Christy; James R Merson; R Brad Jones; Douglas F Nixon; Mario A Ostrowski; Peter T Loudon; Ingrid M Pruimboom-Brees; Neil C Sheppard Journal: J Immunol Date: 2012-06-27 Impact factor: 5.422
Authors: Katerina Gkirtzimanaki; Kalliopi K Gkouskou; Urszula Oleksiewicz; Georgios Nikolaidis; Dimitra Vyrla; Michalis Liontos; Vassiliki Pelekanou; Dimitris C Kanellis; Kostantinos Evangelou; Efstathios N Stathopoulos; John K Field; Philip N Tsichlis; Vassilis Gorgoulis; Triantafillos Liloglou; Aristides G Eliopoulos Journal: Proc Natl Acad Sci U S A Date: 2013-03-26 Impact factor: 11.205