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. 2020 Jan-Dec:19:1533033820983793.
doi: 10.1177/1533033820983793.

Genome-Wide DNA Methylation Pattern of Cancer Stem Cells in Esophageal Cancer

Xiying Yu  1   2 , Ying Teng  3 , Xingran Jiang  4 , Hui Yuan  1   2 , Wei Jiang  1   2
Affiliations

Genome-Wide DNA Methylation Pattern of Cancer Stem Cells in Esophageal Cancer

Xiying Yu et al. Technol Cancer Res Treat. 2020 Jan-Dec.

Abstract

Background: Cancer stem cells (CSCs) are considered the main cause of cancer recurrence and metastasis, and DNA methylation is involved in the maintenance of CSCs. However, the methylation profile of esophageal CSCs remains unknown.

Methods: Side population (SP) cells were isolated from esophageal squamous cell carcinoma (ESCC) cell lines KYSE150 and EC109. Sphere-forming cells were collected from human primary esophageal cancer cells. SP cells and sphere-forming cells were used as substitutes for cancer stem-like cells. We investigated the genome-wide DNA methylation profile in esophageal cancer stem-like cells using reduced representation bisulfite sequencing (RRBS).

Results: Methylated cytosine (mC) was found mostly in CpG dinucleotides, located mostly in the intronic, intergenic, and exonic regions. Forty intersected differentially methylated regions (DMRs) were identified in these 3 groups of samples. Thirteen differentially methylated genes with the same alteration trend were detected; these included OTX1, SPACA1, CD163L1, ST8SIA2, TECR, CADM3, GRM1, LRRK1, CHSY1, PROKR2, LINC00658, LOC100506688, and NKD2. DMRs covering ST8SIA2 and GRM1 were located in exons. These differentially methylated genes were involved in 10 categories of biological processes and 3 cell signaling pathways.

Conclusions: When compared to non-CSCs, cancer stem-like cells have a differential methylation status, which provides an important biological base for understanding esophageal CSCs and developing therapeutic targets for esophageal cancer.

Keywords: DMR; RRBS; cancer stem cells; esophageal cancer; methylome.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Isolation of esophageal cancer stem cells. A. Side population (SP) analysis in KYSE150 and EC109 cell lines. B. Tumor spheres (S1-sphere) formed by primary ESCC cells (S1).
Figure 2.
Figure 2.
Methylation level at different gene locations.
Figure 3.
Figure 3.
Differentially methylated regions (DMRs) analysis. A. The distribution of DMRs. B. The GO analysis of intersect DMRs in these 3 groups of specimens. C. The KEGG analysis of intersected DMRs in these 3 groups.
Figure 4.
Figure 4.
The genes were covered by 40 over-lapped DMRs in these 3 groups. The red represents hypermethylated, and the green represents hypomethylated.
Figure 5.
Figure 5.
Analysis of the hypomethylated genes using GEPIA. A. The mRNA expression of OTX1, CD163L1, and ST8SIA2 in esophageal cancer. B. Expression of LRRK1, NKD2, or ST8SIA2 is correlated with poor diseasefree survival in ESCC.
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