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. 2022 Dec 9;11(24):3989.
doi: 10.3390/cells11243989.

cfDNA Methylation Profiles and T-Cell Differentiation in Women with Endometrial Polyps

Xiao-Hong Li  1 , Mei-Yin Lu  2 , Jia-Li Niu  2 , Dong-Yan Zhu  2 , Bin Liu  2
Affiliations

cfDNA Methylation Profiles and T-Cell Differentiation in Women with Endometrial Polyps

Xiao-Hong Li et al. Cells. .

Abstract

DNA methylation is a part of the regulatory mechanisms of gene expression, including chromatin remodeling and the activity of microRNAs, which are involved in the regulation of T-cell differentiation and function. However, the role of cfDNA methylation in T-cell differentiation is entirely unknown. In patients with endometrial polyps (EPs), we have found an imbalance of T-cell differentiation and an aberrant cfDNA methylation profile, respectively. In this study, we investigated the relationship between cfDNA methylation profiles and T-cell differentiation in 14 people with EPs and 27 healthy controls. We found that several differentially methylated genes (DMGs) were associated with T-cell differentiation in people with EPs (ITGA2-Naïve CD4, r = -0.560, p = 0.037; CST9-EMRA CD4, r = -0.626, p = 0.017; and ZIM2-CM CD8, r = 0.576, p = 0.031), but not in healthy controls (all p > 0.05). When we combined the patients' characteristics, we found a significant association between ITGA2 methylation and polyp diameter (r = 0.562, p = 0.036), but this effect was lost when adjusting the level of Naïve CD4 T-cells (r = 0.038, p = 0.903). Moreover, the circulating sex hormone levels were associated with T-cell differentiation (estradiol-Naïve CD4, r = -0.589, p = 0.027), and the cfDNA methylation profile (testosterone-ZIM2, r = -0.656, p = 0.011). In conclusion, this study has established a link between cfDNA methylation profiles and T-cell differentiation among people with EPs, which may contribute to the etiology of EPs. Further functional studies are warranted.

Keywords: T-cell differentiation; cfDNA; endometrial polyp; etiology; methylation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Comparison of the ratio of Naïve CD4+ T-cells, CM CD4+ T-cells, EMRA CD4+ T-cells, and CM CD8+ T-cells between people with EPs and healthy controls. (A) Percentage of Naïve CD4+ T-cells in CD4+ T-cells; (B) percentage of CM CD4+ T-cells in CD4+ T-cells; (C) percentage of EMRA CD4+ T-cells in CD4+ T-cells; (D) percentage of CM CD8+ T-cells in CD8+ T-cells. *** p < 0.001.
Figure 2
Figure 2
Comparison of methylation levels of ITGA2, CST9, ZIM2, CABP5, CACNA2D4, CTBP1, DLGAP2, E2F3, ESPNP, HDAC4, IGF1R, KCNJ12, NBPF25P, PXDN, RASA3, TCF7L1, TPO, UGT1A8/10, and VAV2 between people with EPs and healthy controls. ** p < 0.01, *** p < 0.001.
Figure 2
Figure 2
Comparison of methylation levels of ITGA2, CST9, ZIM2, CABP5, CACNA2D4, CTBP1, DLGAP2, E2F3, ESPNP, HDAC4, IGF1R, KCNJ12, NBPF25P, PXDN, RASA3, TCF7L1, TPO, UGT1A8/10, and VAV2 between people with EPs and healthy controls. ** p < 0.01, *** p < 0.001.
Figure 3
Figure 3
Correlation between cfDNA methylation and T-cell differentiation in people with EPs and controls. (A) The relationship between the methylation level of ITGA2 and the ratio of Naive CD4+ T-cells in people with EPs. (B) The relationship between the methylation level of ITGA2 and the ratio of Naive CD4+ T-cells in healthy controls. (C) The relationship between the methylation level of CST9 and the ratio of EMRA CD4+ T-cells in people with EPs. (D) The relationship between the methylation level of CST9 and the ratio of EMRA CD4+ T-cells in healthy controls. (E) The relationship between the methylation level of ZIM2 and the ratio of CM CD8+ T-cells in people with EPs. (F) The relationship between the methylation level of ZIM2 and the ratio of CM CD8+ T-cells in healthy controls.
Figure 3
Figure 3
Correlation between cfDNA methylation and T-cell differentiation in people with EPs and controls. (A) The relationship between the methylation level of ITGA2 and the ratio of Naive CD4+ T-cells in people with EPs. (B) The relationship between the methylation level of ITGA2 and the ratio of Naive CD4+ T-cells in healthy controls. (C) The relationship between the methylation level of CST9 and the ratio of EMRA CD4+ T-cells in people with EPs. (D) The relationship between the methylation level of CST9 and the ratio of EMRA CD4+ T-cells in healthy controls. (E) The relationship between the methylation level of ZIM2 and the ratio of CM CD8+ T-cells in people with EPs. (F) The relationship between the methylation level of ZIM2 and the ratio of CM CD8+ T-cells in healthy controls.
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