Cải thiện dự đoán rủi ro trong bệnh bạch cầu lympho cấp ở trẻ em thông qua phân tích metyl hóa DNA

Springer Science and Business Media LLC - 2024
Adrián Mosquera Orgueira1,2, Olga Krali3,4, Carlos Pérez Míguez2, Andrés Peleteiro Raíndo1,2, José Ángel Díaz Arias1,2, Marta Sonia González Pérez1,2, Manuel Mateo Pérez Encinas2,1, Manuel Fernández Sanmartín2,5, Daniel Sinnet6,7, Mats Heyman8,9, Gudmar Lönnerholm9,10, Ulrika Norén-Nyström9,11, Kjeld Schmiegelow9,12, Jessica Nordlund4,3
1Department of Hematology, University Hospital of Santiago de Compostela, Compostela, Spain
2Health Research Institute of Santiago de Compostela, Compostela, Spain
3Department of Medical Sciences, Molecular Precision Medicine, Uppsala University, Uppsala, Sweden
4Science for Life Laboratory, Uppsala University, Uppsala, Sweden
5Department of Pediatric Medicine, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
6Research Center, CHU Sainte-Justine, Montréal, Canada
7Department of Pediatrics, Université de Montréal, Montreal, Canada
8Childhood Cancer Research Unit, Karolinska Institutet, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden
9For the Nordic Society of Pediatric Hematology and Oncology (NOPHO), Stockholm, Sweden
10Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
11Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden
12Pediatrics and Adolescent Medicine, Rigshospitalet, and the Medical Faculty, Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

Tóm tắt

Bạch cầu lympho cấp tính (ALL) là loại ung thư phổ biến nhất ở trẻ em, và mặc dù đã đạt được nhiều tiến bộ trong kết quả điều trị, tái phát vẫn là một mối nguy lớn đối với tỷ lệ tử vong và các biến chứng lâu dài. Để giải quyết thách thức này, chúng tôi đã sử dụng một kỹ thuật học máy có giám sát, cụ thể là rừng sống ngẫu nhiên, để dự đoán nguy cơ tái phát và tử vong dựa trên dữ liệu metyl hóa DNA từ một nhóm 763 bệnh nhân ALL trẻ em được điều trị tại các nước Bắc Âu. Dự đoán nguy cơ tái phát (RRP) được xây dựng dựa trên 16 vị trí CpG, cho thấy chỉ số c-index lần lượt là 0.667 và 0.677 trong các tập huấn luyện và kiểm tra. Dự đoán nguy cơ tử vong (MRP), bao gồm 53 vị trí CpG, thể hiện chỉ số c-index là 0.751 và 0.754 trong các tập huấn luyện và kiểm tra, tương ứng. Để xác thực giá trị dự đoán của các chỉ số, chúng tôi đã phân tích thêm hai nhóm độc lập của bệnh nhân ALL Canada (n = 42) và Bắc Âu (n = 384). Việc xác thực bên ngoài đã xác nhận những phát hiện của chúng tôi, với RRP đạt c-index 0.667 trong nhóm Canada, và RRP và MRP đạt chỉ số c-index lần lượt là 0.529 và 0.621 trong một nhóm Bắc Âu độc lập. Độ chính xác của các mô hình RRP và MRP đã được cải thiện khi kết hợp dữ liệu nhóm rủi ro truyền thống, nhấn mạnh tiềm năng tích hợp đồng bộ các yếu tố tiên đoán lâm sàng. Mô hình MRP cũng cho phép xác định một nhóm rủi ro có tỷ lệ tái phát và tử vong cao. Kết quả của chúng tôi cho thấy tiềm năng của metyl hóa DNA như một yếu tố dự đoán và một công cụ để tinh chỉnh phân tầng rủi ro trong bệnh ALL trẻ em. Điều này có thể dẫn đến các chiến lược điều trị cá nhân hóa dựa trên hồ sơ epigenetic.

Từ khóa

#Bạch cầu lympho cấp tính #metyl hóa DNA #dự đoán rủi ro #chiến lược điều trị cá nhân hóa #học máy có giám sát.

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