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Wang, Y.* ; Deng, H.* ; Xin, S. ; Zhang, K.* ; Shi, R.* ; Bao, X.

Prognostic and predictive value of three DNA methylation signatures in lung adenocarcinoma.

Front. Genet. 10:349 (2019)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Background: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related mortality worldwide. Molecular characterization-based methods hold great promise for improving the diagnostic accuracy and for predicting treatment response. The DNA methylation patterns of LUAD display a great potential as a specific biomarker that will complement invasive biopsy, thus improving early detection. Method: In this study, based on the whole-genome methylation datasets from The Cancer Genome Atlas (TCGA) and several machine learning methods, we evaluated the possibility of DNA methylation signatures for identifying lymph node metastasis of LUAD, differentiating between tumor tissue and normal tissue, and predicting the overall survival (OS) of LUAD patients. Using the regularized logistic regression, we built a classifier based on the 3616 CpG sites to identify the lymph node metastasis of LUAD. Furthermore, a classifier based on 14 CpG sites was established to differentiate between tumor and normal tissues. Using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression, we built a 16-CpG-based model to predict the OS of LUAD patients. Results: With the aid of 3616-CpG-based classifier, we were able to identify the lymph node metastatic status of patients directly by the methylation signature from the primary tumor tissues. The 14-CpG-based classifier could differentiate between tumor and normal tissues. The area under the receiver operating characteristic (ROC) curve (AUC) for both classifiers achieved values close to 1, demonstrating the robust classifier effect. The 16-CpG-based model showed independent prognostic value in LUAD patients. Interpretation: These findings will not only facilitate future treatment decisions based on the DNA methylation signatures but also enable additional investigations into the utilization of LUAD DNA methylation pattern by different machine learning methods.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Dna Methylation ; Lasso Cox Regression ; Luad ; Metastasis ; Recursive Feature Elimination ; Regularized Logistic Regression; Gene-expression; Cancer; Egfr; Epidemiology; Inactivation; Association; Mutations; Diagnosis; Survival; Head
ISSN (print) / ISBN 1664-8021
e-ISSN 1664-8021
Zeitschrift Frontiers in Genetics
Quellenangaben Band: 10, Heft: , Seiten: , Artikelnummer: 349 Supplement: ,
Verlag Frontiers
Verlagsort Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Biology (ISB)
Institute of Molecular Toxicology and Pharmacology (TOXI)