Xác định các gen và con đường chủ chốt trong ung thư đại trực tràng liên quan đến viêm đại tràng bằng phân tích thông tin sinh học tích hợp

BMC Genomic Data - Tập 23 - Trang 1-13 - 2022
Yongming Huang1, Xiaoyuan Zhang2, PengWang1, Yansen Li1, Jie Yao3
1Department of General Surgery, Affiliated Hospital of Jining Medical University, Jining, China
2Key Laboratory of Precision Oncology in Universities of Shandong, Department of Pathology and Institute of Precision Medicine, Taibai Lake New Area, Jining Medical University, Jining, China
3Department of Oncology, Jining Hospital of Traditional Chinese Medicine, Jining, China

Tóm tắt

Bệnh nhân ung thư đại trực tràng liên quan đến viêm đại tràng (CAC) có độ tuổi khởi phát trẻ hơn, có nhiều tổn thương và khối u xâm lấn hơn so với bệnh nhân ung thư đại trực tràng rải rác. Việc phát hiện sớm CAC bằng nội soi là một thách thức, và tỷ lệ mắc ung thư đại trực tràng phân chia vẫn còn cao. Do đó, việc xác định các biomarker có thể dự đoán quá trình hình thành khối u của CAC là cực kỳ cần thiết. Tổng cộng 275 gen biểu hiện khác biệt (DEGs) đã được xác định trong CAC. IGF1, BMP4, SPP1, APOB, CCND1, CD44, PTGS2, CFTR, BMP2, KLF4 và TLR2 được xác định là các DEGs chủ chốt, những gen này đã được làm giàu đáng kể trong các con đường PI3K-Akt, quy định đa năng tế bào gốc, gắn kết điểm, tín hiệu Hippo và tín hiệu AMPK. Biểu đồ Sankey cho thấy rằng các gen của cả con đường tín hiệu PI3K-AKT và gắn kết điểm đều được biểu hiện cao hơn (ví dụ, SPP1, CD44, TLR2, CCND1 và IGF1), và các gen biểu hiện cao hơn được dự đoán là bị điều chỉnh bởi các miRNA quan trọng: hsa-mir-16-5p, hsa-mir-1-3p, v.v.. Mạng lưới gen chủ chốt - yếu tố phiên mã (TFs) tiết lộ FOXC1 là một yếu tố phiên mã cốt lõi. Ở bệnh nhân viêm đại tràng loét (UC), KLF4, CFTR, BMP2, TLR2 cho thấy biểu hiện thấp hơn đáng kể trong ung thư liên quan đến UC. BMP4 và IGF1 cho thấy biểu hiện cao hơn ở UT-Ca so với niêm mạc không khối u. Phân tích sống sót cho thấy rằng sự biểu hiện khác biệt của SPP1, CFTR và KLF4 có liên quan đến tiên lượng xấu trong ung thư đại trực tràng. Nghiên cứu của chúng tôi cung cấp những cái nhìn mới về cơ chế phát triển của CAC. Các gen chủ chốt và các con đường tín hiệu có thể góp phần vào việc phòng ngừa, chẩn đoán và điều trị CAC.

Từ khóa


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