CHST7 Methylation Status Related to the Proliferation and Differentiation of Pituitary Adenomas

Abstract

Pituitary adenomas (PAs) are the second most common primary brain tumor and may develop from any of the cell lineages responsible for producing the different pituitary hormones. DNA methylation is one of the essential epigenetic mechanisms in cancers, including PAs. In this study, we measured the expression profile and promoter methylation status of carbohydrate sulfotransferase 7 (CHST7) in patients with PA; then, we investigated the effect of the CHST7 methylation status on the proliferation and differentiation of PAs. The volcano map and Metascape results showed that the levels of CHST7 were related to the lineages’ differentiation and the cell adhesion of PAs, and patients with low CHST7 had greater chances of having an SF-1 lineage (p = 0.002) and optic chiasm compression (p = 0.007). Reactome pathway analysis revealed that most of the DEGs involved in the regulation of TP53 regulated the transcription of cell cycle genes (HSA-6791312 and HSA6804116) in patients with high CHST7. Correlation analysis showed that CHST7 was significantly correlated with the eIF2/ATF4 pathway and mitochondrion-related genes. The AUC of ROC showed that CHST7 (0.288; 95% CI: 0.187–0.388) was superior to SF-1 (0.555; 95% CI: 0.440–0.671) and inferior to FSHB (0.804; 95% CI: 0.704–0.903) in forecasting the SF-1 lineage (p < 0.001). The SF-1 lineage showed a higher methylation frequency for CHST7 than the Pit-1 and TBX19 lineages (p = 0.009). Furthermore, as the key molecule of the hypothalamic–pituitary–gonadal axis, inhibin βE (INHBE) was positively correlated with the levels of CHST7 (r = 0.685, p < 0.001). In summary, CHST7 is a novel pituitary gland specific protein in SF-1 lineage adenomas with a potential role in gonadotroph cell proliferation and lineage differentiation in PAs.

CircDDX17 inhibits invasive progression of pituitary adenomas by sponging miR-1279 and regulating CADM2 expression

“…Similar to other cancers, multiple risk genes for PA have been reported in the previous documents. CHST7 is a novel pituitary gland specific protein in SF-1 lineage adenomas with a potential role in gonadotroph cell proliferation and lineage differentiation in PA (13). Programmed cell death 10 (PDCD10) can induce aggressive behaviors of PAs by promoting cellular proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) through CXC motif chemokine receptor 2 (CXCR2)-AKT/extracellular regulated protein kinase (ERK) signaling axis (14).…”

Carbohydrate sulfotransferases

“…Carbohydrate sulfotransferase 7 controls the CSPG concentrations, which contribute to metastatic processes and carcinogenesis (73,74). Deoxyribonucleic acid methylation of the CHST7 gene, determined by the methylation-sensitive high-resolution melting (MS HRM), was linked to the pituitary tumour and colon cancer development (75,76). Hypermethylation of CHST7 found in pituitary adenomas was associated with tumour proliferation (N = 106, P = 0.026) (75).…”

“…Deoxyribonucleic acid methylation of the CHST7 gene, determined by the methylation-sensitive high-resolution melting (MS HRM), was linked to the pituitary tumour and colon cancer development (75,76). Hypermethylation of CHST7 found in pituitary adenomas was associated with tumour proliferation (N = 106, P = 0.026) (75). A similar result was obtained in the evaluation of CHST7 role in colorectal cancer.…”