No 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.

The RNA-binding protein LIN28B is an important factor for cell proliferation. Because LIN28B polymorphisms have been shown to be relative with the recurrence of some hyperplastic diseases, we hypothesized that genetic variants of LIN28B gene were associated with postoperative recurrence risk in reproductive-age women with endometrial polyps (EP). In a hospital-based cohort of 351 reproductive female patients underwent hysteroscopic polypectomies between May 2018 and Jan 2020, we genotyped two common polymorphisms in LIN28B gene ( rs 369065   C > T and rs 314280   A > G ) and analyzed their associations with the risk of postoperative recurrence in multiple Cox regression model. When followed up to Jun 2021, carries of rs369065 TT genotype had an increased risk of polyp recurrence (adjusting hazard ratio HR = 1.883 , 95% confidence interval CI = 1.033 − 3.434 ) and had a shorter time to recurrence (median time 352 vs. 342 days, log-rank P < 0.01 ), compared to the CC/CT genotype. Further stratification analysis showed that the increased risk of rs369065 TT genotype was more evident in patients who were older than 33 years (adjusted HR = 2.597 , 95 % CI = 1.037 − 6.505 ), had a single polyp (adjusted HR = 2.545 , 95 % CI = 1.059 − 6.113 ), and had smaller polyps (<1.2 cm, adjusted HR = 2.708 , 95 % CI = 1.042 − 7.043 ). However, no significant association between rs 314280   A > G polymorphism and the risk of polyp recurrence was found. Our study suggests that rs369065 TT genotype of LIN28B gene is associated with an increased postoperative recurrence risk in EP patients, especially in those with fewer and smaller polyps. These findings implicate a precise choice of clinical counseling and decision making. Larger studies in different ethnic populations are warranted.