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Xác định các dấu ấn sinh học liên quan đến mitophagy và sự xâm nhập của tế bào miễn dịch trong rối loạn trầm cảm lớn
Tóm tắt
Rối loạn trầm cảm lớn (MDD) là một tình trạng sức khỏe tâm thần có thể đe dọa tính mạng và gây tàn phế. Mitophagy, một hình thức tự thực bào chọn lọc loại bỏ ty thể bị rối loạn chức năng, có liên quan đến trầm cảm. Tuy nhiên, các nghiên cứu về mối quan hệ giữa các gen liên quan đến mitophagy (MRGs) và MDD rất hạn chế. Nghiên cứu này nhằm xác định các dấu ấn sinh học có liên quan đến mitophagy cho MDD và mô tả các cơ chế phân tử cơ bản. Các hồ sơ biểu hiện gen của 144 mẫu MDD và 72 mẫu kiểm soát bình thường đã được truy xuất từ cơ sở dữ liệu Gene Expression Omnibus, và các gen MRGs đã được trích xuất từ cơ sở dữ liệu GeneCards. Phân cụm đồng thuận được sử dụng để xác định các cụm MDD. Sự xâm nhập của tế bào miễn dịch được đánh giá bằng cách sử dụng CIBERSORT. Phân tích làm giàu chức năng được thực hiện để xác định ý nghĩa sinh học của các gen biểu hiện khác biệt liên quan đến mitophagy (MR-DEGs). Phân tích mạng lưới đồng biểu hiện gen có trọng số, cùng với mạng lưới tương tác protein-protein (PPI), đã được sử dụng để xác định các mô-đun chính và các gen trung tâm. Dựa trên phân tích nhà điều hành co-giảm và phân tích hồi quy Cox đơn biến, một mô hình chẩn đoán đã được xây dựng và đánh giá bằng các đường cong đặc tính hoạt động nhận biết và được xác thực bằng dữ liệu huấn luyện và dữ liệu xác thực bên ngoài. Chúng tôi đã phân loại lại MDD thành hai kiểu phân tử theo các dấu ấn sinh học và đánh giá mức độ biểu hiện của chúng. Tổng cộng, 315 MR-DEGs liên quan đến MDD đã được xác định. Các phân tích làm giàu chức năng cho thấy rằng MR-DEGs chủ yếu giàu có trong các quá trình sinh học liên quan đến mitophagy và nhiều con đường bệnh thoái hóa thần kinh. Hai cụm riêng biệt với các đặc điểm xâm nhập miễn dịch khác nhau đã được xác định trong 144 mẫu MDD. MATR3, ACTL6A, FUS, BIRC2 và RIPK1 đã được xác định là các dấu ấn sinh học tiềm năng của MDD. Tất cả các dấu ấn sinh học đều cho thấy mối tương quan khác nhau với các tế bào miễn dịch. Ngoài ra, hai kiểu phân tử với chữ ký gen mitophagy khác biệt đã được xác định. Chúng tôi đã xác định một chữ ký gen năm gen MRG mới có hiệu suất chẩn đoán xuất sắc và xác định mối liên hệ giữa các MRG và môi trường vi mô miễn dịch trong MDD.
Từ khóa
#Rối loạn trầm cảm lớn #Mitophagy #Dấu ấn sinh học #Tế bào miễn dịch #Chẩn đoánTài liệu tham khảo
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