Alterations of DNA methylation were associated with the rapid growth of cortisol-producing adrenocortical adenoma during pregnancy

Cortisol-producing adrenocortical adenoma (CPA) during pregnancy rarely occurs in clinic. Growing evidence suggests that DNA methylation plays a key role in adrenocortical adenomas. The present study aims to examine the genome-wide DNA methylation profiles and identify the differences in DNA methylation signatures of non-pregnant and pregnant patients with CPA.

Genome-wide DNA methylation profiling of CPA in non-pregnant and pregnant patients was identified in the present study. Alterations of DNA methylation were associated with the pathogenesis and exacerbation of CPA during pregnancy.

Four pregnant and twelve non-pregnant patients with CPA were enrolled. The pregnant patients with CPA had higher serum cortisol, Estradiol, Progesterone, and human chorionic gonadotropin concentration, while having lower serum FSH (follicle-stimulating hormone) and luteinizing hormone concentrations (P < 0.01). Compared with the non-pregnant patients, the duration is shorter, and the growth rate of the tumor is faster in pregnant patients with CPA (P < 0.05). Morphology and cell proliferation assay showed that the percentage of Ki-67 positive cells in CPA were higher in pregnant group than non-pregnant group (8.0% vs 5.5%, P < 0.05). The DNA methylation analysis showed that Genome-wide DNA methylation signature difference between pregnant and non-pregnant with CPA, that the pregnant group had more hypermethylated DMPs (67.94% vs 22.16%) and less hypomethylated DMPs (32.93% vs 77.84%). The proportion of hypermethylated DMPs was relatively high on chromosomes 1 (9.68% vs 8.67%) and X (4.99% vs 3.35%) but lower on chromosome 2(7.98% vs 12.92%). In pregnant patients with CPA, 576 hypomethylated DMPs and 1109 hypermethylated DMPs were identified in the DNA promoter region. Bioinformatics analysis indicated that the Wnt/β-Catenin pathway, Ras/MAPK Pathway and PI3K-AKT Pathway were associated with the development of CPA during pregnancy. Conclusions: Genome-wide DNA methylation profiling of CPA in non-pregnant and pregnant patients was identified in the present study. Alterations of DNA methylation were associated with the pathogenesis and exacerbation of CPA during pregnancy.