Yonsei Med J.  2020 Dec;61(12):1013-1023. 10.3349/ymj.2020.61.12.1013.

Screening of Methylation Gene Sites as Prognostic Signature in Lung Adenocarcinoma

• Dong M
• Yang Z
• Li X
• Zhang Z
• Yin A

• KMID: 2508966
• DOI: http://doi.org/10.3349/ymj.2020.61.12.1013

Abstract

Purpose
Most lung adenocarcinoma (LUAD) patients are diagnosed at the advanced stage and have poor prognosis. DNA methylation plays an important role in the prognosis prediction of cancers. The objective of this study was to identify new DNA methylation sites as biomarkers for LUAD prognosis.
Materials and Methods
We downloaded DNA methylation data from The Cancer Genome Atlas data portal. Cox proportional hazard regression model and random survival forest algorithm were applied to identify the DNA-methylation sites. Methylation of sites were validated in the Gene Expression Omnibus cohorts. Function annotation were done to explore the biological function of DNA methylated sites signature.
Results
Six DNA methylation sites were identified as prognosis signature. The signature yielded acceptable discrimination between the high-risk group and low-risk group. The discrimination effect of this DNA methylation signature for the OS was obvious, with a median OS of 21.89 months vs. 17.74 months for high-risk vs. low-risk groups. This prognostic prediction model was validated by the test group and GEO dataset. The predictive survival value was higher for the prognostic prediction model than that for the tumor node metastasis stage. Adjuvant hemotherapy could not affect the prediction of the signature. Functional analysis indicated that these signature genes were involved in protein binding and cytoplasm.
Conclusion
We identified the prognostic signature for LUAD by combining six DNA methylation sites. This could service as potential robust and specificity signature in the prognosis prediction of LUAD.

Keyword

Lung adenocarcinoma; prognosis signature; methylation; TCGA