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
| Autor: | Kim-Wanner, S.Z., Assenov, Y., Nair, M.B., Weichenhan, D., Benner, A., Becker, N., Landwehr, K., Kuner, R., Sültmann, H., Esteller, M., Koch, I., Lindner, M., Meister, M., Thomas, M., Bieg, M., Klingmüller, U., Schlesner, M., Warth, A., Brors, B., Seifried, E., Bönig, H., Plass, C., Risch, A., Muley, T., Universitat Autònoma de Barcelona |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Oncology Lung adenocarcinoma medicine.medical_specialty Lung Neoplasms ADN Adenocarcinoma of Lung Methylation profiling medicine.disease_cause Methylation 03 medical and health sciences 0302 clinical medicine Prognostic marker PLUT Internal medicine Biomarkers Tumor Humans Medicine ddc:610 Promoter Regions Genetic business.industry Hazard ratio Promoter DNA DNA Methylation Prognosis medicine.disease Long non-coding RNA 030104 developmental biology Differentially methylated regions 030220 oncology & carcinogenesis IncRNA Càncer de pulmó Biomarker (medicine) Adenocarcinoma RNA Long Noncoding Neoplasm Recurrence Local Lung cancer business Carcinogenesis Metilació |
| Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Dipòsit Digital de la UB Universidad de Barcelona Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) Recercat. Dipósit de la Recerca de Catalunya instname |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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