Abstract
As a noninvasive blood testing, the detection of cell-free DNA (cfDNA) methylation in plasma has raised an increasing interest due to diagnostic applications. Although extensively used in cfDNA methylation analysis, bisulfite sequencing is less cost-effective. In this study, we investigated the cfDNA methylation patterns in lung cancer patients by MeDIP-seq. Compared with the healthy individuals, 330 differentially methylated regions (DMRs) at gene promoters were identified in lung cancer patients with 33 hypermethylated and 297 hypomethylated regions, respectively. Moreover, these hypermethylated genes were validated with the publicly available DNA methylation data, yielding a set of ten significant differentially methylated genes in lung cancer, including B3GAT2, BCAR1, HLF, HOPX, HOXD11, MIR1203, MYL9, SLC9A3R2, SYT5, and VTRNA1-3. Our study demonstrated MeDIP-seq could be effectively used for cfDNA methylation profiling and identified a set of potential biomarker genes with clinical application for lung cancer.
Highlights
Lung cancer is one of the major cancer types causing cancer deaths [1]
Our results indicate that MeDIP-seq could be effectively used in cell-free DNA (cfDNA) methylation profiling in cancer patients
We found that genes derived from hypermethylated differentially methylated regions (DMRs) are enriched in tumorigenesis-related Gene ontology (GO) items, such as oncostatin-Mmediated signaling pathway, negative regulation of gene silencing by miRNA, negative regulation of posttranscriptional gene silencing, cell adhesion, and DNA replicationdependent nucleosome assembly (Table S4)
Summary
Lung cancer is one of the major cancer types causing cancer deaths [1]. The unavailability of genetic testing for early cancer diagnosis has been regarded as the major cause of high mortality rate [2, 3]. DNA methylation pattern in plasma cfDNA is similar with that derived from cancer tissue [5, 13]. These observations suggest that cfDNA methylation could serve as a useful biomarker for cancer detection [14]. Extensively used in cfDNA methylation profiling analysis, bisulfite sequencing is less cost-effective [16]. Disease Markers (MeDIP-seq), a genome-wide scale and cost-effective method, has been extensively used in genomic DNA methylome analysis, whereas it is rarely applied in characterizing cfDNA methylation [15]. Our results indicate that MeDIP-seq could be effectively used in cfDNA methylation profiling in cancer patients
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