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000154460 1001_ $$0P:(DE-HGF)0$$aKim-Wanner, Soo-Zin$$b0$$eFirst author
000154460 245__ $$aGenome-wide DNA methylation profiling in early stage I lung adenocarcinoma reveals predictive aberrant methylation in the promoter region of the long non-coding RNA PLUT - an exploratory study.
000154460 260__ $$aAmsterdam$$bElsevier$$c2020
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000154460 520__ $$aSurgery is the treatment of choice in early stage I lung adenocarcinoma. However, a considerable portion of patients experience recurrence within the first two years following complete resection. Especially suitable prognostic biomarkers are not available that identify patients at high risk for recurrence who may probably benefit from adjuvant treatment. This study aimed to identify methylation markers for early recurrence that may become important tools for the development of new treatment modalities.Genome-wide DNA methylation profiling was performed on 30 stage I lung adenocarcinomas comparing 14 patients with early metastatic recurrence to 16 patients with a long-term relapse-free survival period using methylated-CpG-immunoprecipitation (MCIp) followed by high-throughput next generation sequencing. The differentially methylated regions (DMRs) between the two subgroups were validated for their prognostic value in two independent cohorts using the MassCleave Assay, a high-resolution quantitative methylation analysis.Unsupervised clustering of patients in the discovery cohort based on DMRs identified patients with shorter relapse free survival (HR 2.23; 95% CI 0.66 to 7.53; p=0.03). In two validation cohorts promoter hypermethylation of the long non-coding RNA (lncRNA) PLUT was significantly associated with shorter relapse free survival (HR 0.54; 95% CI 0.31 to 0.93; p<0.026) and could be shown to be an independent prognostic factor in the multivariate cox regression analysis.Promoter hypermethylation of the lncRNA PLUT is predictive in patients with early stage I adenocarcinoma at high risk for early recurrence. Further studies are needed to validate its role in carcinogenesis and its use as a biomarker to facilitate patient selection and risk stratification.
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000154460 7001_ $$0P:(DE-He78)ff4024f7bc236e7897d9c18ee19c451f$$aWeichenhan, Dieter$$b3$$udkfz
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000154460 7001_ $$0P:(DE-He78)ecb33fb615e08035fdcefcaebfdff8f0$$aBecker, Natalia$$b5
000154460 7001_ $$aLandwehr, Katharina$$b6
000154460 7001_ $$0P:(DE-HGF)0$$aKuner, Ruprecht$$b7
000154460 7001_ $$0P:(DE-He78)7483734fd8ab316391aa604c95f0e98a$$aSültmann, Holger$$b8$$udkfz
000154460 7001_ $$aEsteller, Manel$$b9
000154460 7001_ $$aKoch, Ina$$b10
000154460 7001_ $$aLindner, Michael$$b11
000154460 7001_ $$aMeister, Michael$$b12
000154460 7001_ $$aThomas, Michael$$b13
000154460 7001_ $$0P:(DE-He78)e247efc0264a7b0e4bae09804002d4e1$$aBieg, Matthias$$b14$$udkfz
000154460 7001_ $$0P:(DE-HGF)0$$aKlingmueller, Ursula$$b15
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000154460 7001_ $$aWarth, Arne$$b17
000154460 7001_ $$0P:(DE-He78)fc949170377b58098e46141d95c72661$$aBrors, Benedikt$$b18$$udkfz
000154460 7001_ $$aSeifried, Erhard$$b19
000154460 7001_ $$aBonig, Halvard$$b20
000154460 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b21$$udkfz
000154460 7001_ $$0P:(DE-He78)4981f4ef151aea881f38b33df8e35a21$$aRisch, Angela$$b22$$udkfz
000154460 7001_ $$aMuley, Thomas$$b23
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