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Xác định các gen biểu hiện khác biệt methyl hóa chính trong ependymoma hố sau dựa trên phân tích epigenome và transcriptome
Tóm tắt
Ependymoma hố sau (EPN-PF) có thể được phân loại thành Ependymoma hố sau nhóm A (EPN-PFA) và Ependymoma hố sau nhóm B (EPN-PFB) dựa trên trạng thái hồ sơ methyl hóa DNA CpG island và biểu hiện gen. EPN-PFA thường xảy ra ở trẻ em dưới 5 tuổi và có tiên lượng kém. Sử dụng dữ liệu vi mạch epigenome và transcriptome, một phân tích mạng đồng biểu hiện gen có trọng số đa thành phần (WGCNA) đã được sử dụng để xác định hệ thống các gen trung tâm của EPN-PF. Chúng tôi đã tải xuống hai tập dữ liệu vi mạch (GSE66354 và GSE114523) từ cơ sở dữ liệu Gene Expression Omnibus (GEO). Gói Limma R được sử dụng để xác định các gen biểu hiện khác biệt (DEGs), và ChAMP R được sử dụng để phân tích các gen methyl hóa khác biệt (DMGs) giữa EPN-PFA và EPN-PFB. Các phân tích làm giàu GO và KEGG đã được thực hiện bằng cách sử dụng cơ sở dữ liệu Metascape. Phân tích GO cho thấy rằng các gen được làm giàu có sự làm giàu đáng kể trong tổ chức ma trận ngoại bào, phản ứng miễn dịch thích ứng, bè màng, liên kết điểm, con đường NF-kappa B, và hướng dẫn trục. Thông qua WGCNA, chúng tôi phát hiện rằng MEblue có mối tương quan đáng kể với EPN-PF (R = 0.69, P = 1 × 10–08) và đã chọn 180 gen trung tâm trong mô hình màu xanh. Bằng cách so sánh DEGs, DMGs và gen trung tâm trong mạng đồng biểu hiện, chúng tôi đã xác định năm gen hypermethylated, biểu hiện thấp trong EPN-PFA (ATP4B, CCDC151, DMKN, SCN4B, và TUBA4B), và ba trong số đó đã được xác nhận bằng IHC. Phân tích ssGSEA và GSVA cho thấy rằng năm gen trung tâm này có thể dẫn đến tiên lượng kém bằng cách kích hoạt các con đường hypoxia, PI3K-Akt-mTOR, và TNFα-NFKB. Nghiên cứu sâu hơn về các gen trung tâm bị dysmethylated trong EPN-PF và các con đường mà chúng tham gia có thể cung cấp những ý tưởng mới cho điều trị EPN-PF.
Từ khóa
#Ependymoma hố sau #methyl hóa DNA #phân tích epigenome #WGCNA #gen biểu hiện khác biệtTài liệu tham khảo
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