Methylation of L1RE1, RARB, and RASSF1 function as possible biomarkers for the differential diagnosis of lung cancer

PloS One
R F H WalterG Johnen

Abstract

Lung cancer is the major cause of cancer-related deaths worldwide. Differential diagnosis can be difficult, especially when only small samples are available. Epigenetic changes are frequently tissue-specific events in carcinogenesis and hence may serve as diagnostic biomarkers. 138 representative formalin-fixed, paraffin-embedded (FFPE) tissues (116 lung cancer cases and 22 benign controls) were used for targeted DNA methylation analysis via pyrosequencing of ten literature-derived methylation markers (APC, CDH1, CDKN2A, EFEMP1, FHIT, L1RE1, MGMT, PTEN, RARB, and RASSF1). Methylation levels were analyzed with the Classification and Regression Tree Algorithm (CART), Conditional Interference Trees (ctree) and ROC. Validation was performed with additional 27 lung cancer cases and 38 benign controls. TCGA data for 282 lung cancer cases was included in the analysis. CART and ctree analysis identified the combination of L1RE1 and RARB as well as L1RE1 and RASSF1 as independent methylation markers with high discriminative power between tumor and benign tissue (for each combination, 91% specificity and 100% sensitivity). L1RE1 methylation associated significantly with tumor type and grade (p<0.001) with highest methylation in the contr...Continue Reading

References

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Citations

Mar 29, 2019·Journal of Clinical Medicine·Fiorella CalabresePaul Hofman
Sep 25, 2019·Journal of Clinical Medicine·Sandra P NunesCarmen Jerónimo
Aug 17, 2018·The Journal of Clinical Endocrinology and Metabolism·Juliane LippertCristina L Ronchi
Aug 16, 2019·Archives of Biochemistry and Biophysics·Jennifer L MeitzlerJames H Doroshow
Mar 5, 2021·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Lea M SchottenFiliz Oezkan

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Methods Mentioned

BETA
biopsies
PCR
electrophoresis
Methylation

Software Mentioned

R
CART
rpart

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