Tuberc Respir Dis.  2019 Apr;82(2):126-132. 10.4046/trd.2018.0042.

Identification of Serial DNA Methylation Changes in the Blood Samples of Patients with Lung Cancer

• Moon DH
• Kwon SO
• Kim WJ
• Hong Y

• KMID: 2453982
• DOI: http://doi.org/10.4046/trd.2018.0042

Abstract

BACKGROUND
The development of lung cancer results from the interaction between genetic mutations and dynamic epigenetic alterations, although the exact mechanisms are not completely understood. Changes in DNA methylation may be a promising biomarker for early detection and prognosis of lung cancer. We evaluated the serial changes in genome-wide DNA methylation patterns in blood samples of lung cancer patients.
METHODS
Blood samples were obtained for three consecutive years from three patients (2 years before, 1 year before, and after lung cancer detection) and from three control subjects (without lung cancer). We used the MethylationEPIC BeadChip method, which covers the 850,000 bp cytosine-phosphate-guanine (CpG) site, to conduct an epigenome-wide analysis. Significant differentially methylated regions (DMRs) were identified using p-values <0.05 in a correlation test identifying serial methylation changes and serial increase or decrease in β value above 0.1 for three consecutive years.
RESULTS
We found three significant CpG sites with differentially methylated β values and 7,105 CpG sites with significant correlation from control patients without lung cancer. However, there were no significant DMRs. In contrast, we found 11 significant CpG sites with differentially methylated β values and 10,562 CpG sites with significant correlation from patients with lung cancer. There were two significant DMRs: cg21126229 (RNF212) and cg27098574 (BCAR1).
CONCLUSION
This study revealed DNA methylation changes that might be implicated in lung cancer development. The DNA methylation changes may be the possible candidate target regions for the early detection and prevention of lung cancer.

Keyword

DNA Methylation; Lung Neoplasms; Biomarkers

MeSH Terms

Biomarkers
DNA Methylation*
DNA*
Epigenomics
Humans
Lung Neoplasms*
Lung*
Methods
Methylation
Prognosis
Biomarkers
DNA

Figure

• 

  Figure 1 Blood samples were obtained for three consecutive years from three patients with non-small-cell lung cancer or control subjects and analyzed by delta mean and correlation test. Significant β changes were defined as when the delta mean of trait 2–1 and 3–2 was increased (≥0.1) or decreased (≤??.1), and significant correlation was defined when the p-value for the correlation test was >0.05. When both conditions were satisfied, significant differentially-methylated regions were obtained. dm: delta mean.

• 

  Figure 2 Significant differentially methylated regions with significant β changes and correlation. dm0.1, significant β changes of the delta mean with increased (≥0.1) or decreased (≤−0.1); cor0.05, significant correlation with p-value of >0.05.

• 

  Figure 3 Clustering heatmap of three patients with lung cancer. dm0.1, significant β changes of the delta mean with increased (≥0.1) or decreased (≤−0.1); cor0.05, significant correlation with p-value of >0.05.

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