Chữ ký PAM50 dựa trên nghiên cứu và khả năng sống sót lâu dài ở bệnh nhân ung thư vú

Springer Science and Business Media LLC - 2020
Minya Pu1, Karen Messer2, Sherri R. Davies3, Tammi L. Vickery4, Emily Pittman1, Barbara A. Parker5, Matthew J. Ellis6, Shirley W. Flatt1, Catherine R. Marinac7, Sandahl H Nelson8, Elaine R. Mardis9, John P. Pierce2, Loki Natarajan2
1Moores Cancer Center, University of California, San Diego, San Diego, CA, USA
2Department of Family Medicine and Public Health, University of California, San Diego, 3855 Health Sciences Drive #0901, La Jolla, CA, 92093-0901, USA
3Department of Medicine, Washington University St. Louis, St. Louis, MO, USA
4Washington University St. Louis, McDonnell Genome Institute, St. Louis, MO, USA
5Department of Medicine, University of California, San Diego, San Diego, CA, USA
6Baylor College of Medicine, Lester and Sue Smith Breast Center, Houston, TX, USA
7Division of Population Sciences, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
8Precision for Medicine, San Diego, CA, USA
9Nationwide Children’s Hospital, Institute for Genomic Medicine, Columbus, OH, USA

Tóm tắt

Tóm tắt Mục đích Các chữ ký đa gene cung cấp cái nhìn sinh học và phân tầng nguy cơ trong ung thư vú. Các kiểu phân loại phân tử nội sinh được xác định bởi sự biểu hiện mRNA của 50 gene (PAM50) có giá trị tiên đoán trong ung thư vú dương tính với thụ thể hormone ở phụ nữ mãn kinh. Tuy nhiên, đối với 25-40% trong nhóm nguy cơ trung bình PAM50, nguy cơ lâu dài vẫn không chắc chắn. Nghiên cứu của chúng tôi nhằm (i) kiểm tra giá trị tiên đoán lâu dài của chữ ký PAM50 trong ung thư vú trước và sau mãn kinh; (ii) điều tra xem mô hình PAM50 có thể được cải thiện bằng cách thêm các mRNA khác liên quan đến oncogenesis hay không. Phương pháp Chúng tôi đã sử dụng các mẫu FFPE lưu trữ từ 1723 bệnh nhân sống sót sau ung thư vú; chất lượng đọc cao đã được thu thập trên 1253 mẫu. Biểu hiện của bản sao được định lượng bằng cách sử dụng một bộ mã tùy chỉnh với các đầu dò cho > 100 mục tiêu. Các mô hình Cox đã đánh giá các chữ ký gene cho tình trạng tái phát ung thư vú và sự sống sót. Kết quả Trong hơn 15 năm theo dõi, các kiểu PAM50 có liên quan đến kết quả ung thư vú (P < 0.01) sau khi đã tính đến giai đoạn, grade và tuổi tại thời điểm chẩn đoán. Kết quả không khác biệt theo tình trạng mãn kinh tại thời điểm chẩn đoán. Phụ nữ có kiểu Luminal B (so với Luminal A) có nguy cơ cao hơn > 60%. Việc thêm một chữ ký hypoxia 13 gene đã cải thiện khả năng tiên đoán với nguy cơ cao hơn > 40% giữa tertiles hypoxia cao nhất và thấp nhất. Kết luận Các kiểu phân loại nội sinh PAM50 có khả năng tiên đoán độc lập cho sự sống sót lâu dài ở bệnh nhân ung thư vú, bất kể tình trạng mãn kinh. Việc thêm các chữ ký hypoxia đã cải thiện dự đoán nguy cơ. Nếu được lặp lại, việc tích hợp chữ ký hypoxia 13 gene vào công cụ đánh giá nguy cơ PAM50 hiện có có thể tinh chỉnh phân tầng nguy cơ và làm rõ hơn nữa điều trị cho ung thư vú.

Từ khóa


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