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, S. Z. (German Red Cross Blood Donor Service. Institute of Transfusion Medicine and Immune Hematology of the Goethe University Medical School)
Assenov, Y. (Division of Epigenomics. German Cancer Research Center (Deutsches Krebsforschungszentrum [DKFZ]))
Nair, M. B. (Division of Epigenomics. German Cancer Research Center (Deutsches Krebsforschungszentrum [DKFZ]))
Weichenhan, D. (Division of Epigenomics. German Cancer Research Center (Deutsches Krebsforschungszentrum [DKFZ]))
Benner, Axel (Division of Biostatistics. German Cancer Research Center (DKFZ))
Becker, N. (Division of Biostatistics. German Cancer Research Center (DKFZ))
Landwehr, K. (German Red Cross Blood Donor Service. Institute of Transfusion Medicine and Immune Hematology of the Goethe University Medical School)
Kuner, R. (Translational Oncology at the University Medical Center of Johannes Gutenberg University)
Sültmann, H. (Translational Lung Research Centre Heidelberg. Member of the German Centre for Lung Research (Deutsches Zentrum für Lungenforschung))
Esteller, M. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Koch, I. (Center of Thoracic Surgery. Asklepios Fachkliniken München-Gauting. Ludwig Maximilians University. Gauting; Comprehensive Pneumology Centre Munich. German Centre for Lung Research (Deutsches Zentrum für Lungenforschung))
Lindner, M. (Center of Thoracic Surgery. Asklepios Fachkliniken München-Gauting. Ludwig Maximilians University. Gauting; Comprehensive Pneumology Centre Munich. German Centre for Lung Research (Deutsches Zentrum für Lungenforschung))
Meister, M. (Translational Research Unit. Thoraxklinik at University Hospital Heidelberg)
Thomas, M. (Translational Research Unit. Thoraxklinik at University Hospital Heidelberg)
Bieg, M. (Division of Theoretical Bioinformatics. and Heidelberg Center for Personalized Oncology. German Cancer Research Center (DKFZ))
Klingmüller, U. (Division Systems Biology of Signal Transduction. German Cancer Research Center (DKFZ))
Schlesner, M. (Bioinformatics and Omics Data Analytics. German Cancer Research Center (DKFZ))
Warth, A. (Heidelberg University Hospital (Alemanya))
Brors, Benedikt (Division of Applied Bioinformatics. German Cancer Research Center (DKFZ))
Seifried, E. (German Red Cross Blood Donor Service. Institute of Transfusion Medicine and Immune Hematology of the Goethe University Medical School)
Bönig, H. (German Red Cross Blood Donor Service. Institute of Transfusion Medicine and Immune Hematology of the Goethe University Medical School)
Plass, C. (Translational Lung Research Centre Heidelberg. Member of the German Centre for Lung Research (Deutsches Zentrum für Lungenforschung))
Risch, A. (Universität Salzburg. Cancer Cluster Salzburg)
Muley, T. (Translational Research Unit. Thoraxklinik at University Hospital Heidelberg)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	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.
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	IncRNA ; Lung adenocarcinoma ; Methylation profiling ; PLUT ; Prognostic marker
Published in:	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

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles