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| Home > Publications database > Genome-wide DNA methylation profiling in early stage I lung adenocarcinoma reveals predictive aberrant methylation in the promoter region of the long non-coding RNA PLUT - an exploratory study. |
| Home > Publications database > Genome-wide DNA methylation profiling in early stage I lung adenocarcinoma reveals predictive aberrant methylation in the promoter region of the long non-coding RNA PLUT - an exploratory study. |
| Journal Article | DKFZ-2020-00782 |
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2020
Elsevier
Amsterdam
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Please use a persistent id in citations: doi:10.1016/j.jtho.2020.03.023
Abstract: Surgery is the treatment of choice in early stage I lung adenocarcinoma. However, a considerable portion of patients experience recurrence within the first two years following complete resection. Especially suitable prognostic biomarkers are not available that identify patients at high risk for recurrence who may probably benefit from adjuvant treatment. This study aimed to identify methylation markers for early recurrence that may become important tools for the development of new treatment modalities.Genome-wide DNA methylation profiling was performed on 30 stage I lung adenocarcinomas comparing 14 patients with early metastatic recurrence to 16 patients with a long-term relapse-free survival period using methylated-CpG-immunoprecipitation (MCIp) followed by high-throughput next generation sequencing. The differentially methylated regions (DMRs) between the two subgroups were validated for their prognostic value in two independent cohorts using the MassCleave Assay, a high-resolution quantitative methylation analysis.Unsupervised clustering of patients in the discovery cohort based on DMRs identified patients with shorter relapse free survival (HR 2.23; 95% CI 0.66 to 7.53; p=0.03). In two validation cohorts promoter hypermethylation of the long non-coding RNA (lncRNA) PLUT was significantly associated with shorter relapse free survival (HR 0.54; 95% CI 0.31 to 0.93; p<0.026) and could be shown to be an independent prognostic factor in the multivariate cox regression analysis.Promoter hypermethylation of the lncRNA 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.
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