Identification and validation of novel DNA methylation markers for early diagnosis of lung adenocarcinoma.

Molecular Oncology
Miao LiYongjun Piao

Abstract

Lung cancer has the highest mortality of all cancers worldwide. Epigenetic alterations have emerged as potential biomarkers for early diagnosis of various cancer tissue types. To identify methylation markers for early diagnosis of lung adenocarcinoma, we aimed to integrate genome-wide DNA methylation and gene expression data from The Cancer Genome Atlas. To this end, we first examined the global DNA methylation pattern of lung adenocarcinoma and investigated the relationship between DNA methylation subtypes and clinical features. We then extracted differentially methylated and expressed genes, and adopted feature selection techniques to determine the final methylation markers. The performance of the markers in predicting lung adenocarcinoma was evaluated on three independent datasets from Gene Expression Omnibus. Protein levels of marker genes were validated by immunohistochemistry, and their biological function was further verified in vivo. We identified three novel methylation markers in lung adenocarcinoma including cg08032924, cg14823851, and cg19161124, mapping to CMTM2, TBX4, and DPP6, respectively. Validating these results on three independent datasets indicated that the three markers can achieve extremely high sensitivi...Continue Reading

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Datasets Mentioned

BETA
GSE85845

Methods Mentioned

BETA
chemical modification
transfection
PCR
bioluminescence imaging
bronchoalveolar lavages

Software Mentioned

edger
IlluminaHumanMethylation450kanno
DAVID functional
Living Image
. R package
weka
ReliefF

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