Genome-Wide DNA Methylation Profiling in Early Stage I Lung Adenocarcinoma Reveals Predictive Aberrant Methylation in the Promoter Region of the Long Noncoding RNA PLUT : An Exploratory Study
Kim-Wanner, Soo-Zin (Deutsches Krebsforschungszentrum (Heidelberg, Alemanya))
Assenov, Yassen (Deutsches Krebsforschungszentrum (Heidelberg, Alemanya))
Nair, Mridul B. (Deutsches Krebsforschungszentrum (Heidelberg, Alemanya))
Weichenhan, Dieter (Deutsches Krebsforschungszentrum (Heidelberg, Alemanya))
Benner, Axel (Deutsches Krebsforschungszentrum (Heidelberg, Alemanya))
Becker, Natalia (Deutsches Krebsforschungszentrum (Heidelberg, Alemanya))
Landwehr, Katharina (Goethe University. Institute of Transfusion Medicine and Immune Hematology (Frankfurt, Alemanya))
Kuner, Ruprecht (Deutsches Krebsforschungszentrum (Heidelberg, Alemanya))
Sültmann, Holger (Deutsches Krebsforschungszentrum (Heidelberg, Alemanya))
Esteller, M (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Koch, Ina (Ludwig-Maximilians-Universität München (Alemanya))
Lindner, Michael (Ludwig-Maximilians-Universität München Alemanya)))
Meister, Michael (Deutsches Zentrum für Lungenforschung (Heidelberg, Alemanya))
Thomas, Michael (Deutsches Zentrum für Lungenforschung (Heidelberg, Alemanya))
Bieg, Matthias (Deutsches Krebsforschungszentrum (Heidelberg, Alemanya))
Klingmüller, Ursula (Deutsches Zentrum für Lungenforschung (Heidelberg, Alemanya))
Schlesner, Matthias (Deutsches Zentrum für Lungenforschung (Heidelberg, Alemanya))
Warth, Arne (University Hospital Heidelberg (Alemanya))
Brors, Benedikt (Deutsches Krebsforschungszentrum (Heidelberg, Alemanya))
Seifried, Erhard (Goethe University. Institute of Transfusion Medicine and Immune Hematology (Frankfurt, Alemanya))
Bönig, Halvard (Goethe University. Institute of Transfusion Medicine and Immune Hematology (Frankfurt Alemanya))
Plass, Christoph (Deutsches Krebsforschungszentrum (Heidelberg, Alemanya))
Risch, Angela (Paris-Lodron University Salzburg. Department of Biosciences (Austria))
Muley, Thomas (Deutsches Zentrum für Lungenforschung (Heidelberg, Alemanya))
Universitat Autònoma de Barcelona

Data:	2020
Resum:	Introduction: Surgical procedure is the treatment of choice in early stage I lung adenocarcinoma. However, a considerable number of patients experience recurrence within the first 2 years after complete resection. Suitable prognostic biomarkers that identify patients at high risk of recurrence (who may probably benefit from adjuvant treatment) are still not available. This study aimed at identifying methylation markers for early recurrence that may become important tools for the development of new treatment modalities. Methods: Genome-wide DNA methylation profiling was performed on 30 stage I lung adenocarcinomas, comparing 14 patients with early metastatic recurrence with 16 patients with a long-term relapse-free survival period using methylated-CpG-immunoprecipitation followed by high-throughput next-generation sequencing. The differentially methylated regions between the two subgroups were validated for their prognostic value in two independent cohorts using the MassCLEAVE assay, a high-resolution quantitative methylation analysis. Results: Unsupervised clustering of patients in the discovery cohort on the basis of differentially methylated regions identified patients with shorter relapse-free survival (hazard ratio: 2. 23; 95% confidence interval: 0. 66-7. 53; p = 0. 03). In two validation cohorts, promoter hypermethylation of the long noncoding RNA PLUT was significantly associated with shorter relapse-free survival (hazard ratio: 0. 54; 95% confidence interval: 0. 31-0. 93; p < 0. 026) and could be reported as an independent prognostic factor in the multivariate Cox regression analysis. Conclusions: Promoter hypermethylation of the long noncoding RNA PLUT is predictive in patients with early stage I adenocarcinoma at high risk for early recurrence. Further studies are needed to validate its role in carcinogenesis and its use as a biomarker to facilitate patient selection and risk stratification.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	IncRNA ; Lung adenocarcinoma ; Methylation profiling ; PLUT ; Prognostic marker
Publicat a:	Journal of thoracic oncology, Vol. 15 Núm. 8 (august 2020) , p. 1338-1350, ISSN 1556-1380

DOI: 10.1016/j.jtho.2020.03.023
PMID: 32272161

13 p, 1.0 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Institut de Recerca contra la Leucèmia Josep Carreras
Articles > Articles de recerca
Articles > Articles publicats