Mức độ angiopoietin-2, VEGF-A và VCAM-1 trong huyết tương như là các dấu hiệu của huyết áp cao do bevacizumab: CALGB 80303 và 90401 (Liên minh)

Angiogenesis - Tập 25 - Trang 47-55 - 2021
Julia C. F. Quintanilha1, Yingmiao Liu2, Amy S. Etheridge1, Akram Yazdani1, Hedy L. Kindler3, William Kevin Kelly4, Andrew B. Nixon2, Federico Innocenti1
1UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, USA
2Duke University School of Medicine, Duke University, Durham, USA
3Department of Medicine, University of Chicago, Chicago, USA
4Department of Medical Oncology, Yale School of Medicine, New Haven, USA

Tóm tắt

Huyết áp cao là một độc tính phổ biến do bevacizumab và các loại thuốc chống tạo mạch khác gây ra. Hiện tại không có dấu hiệu sinh học nào để dự đoán nguy cơ huyết áp cao do bevacizumab. Nghiên cứu này nhằm xác định các protein trong huyết tương có liên quan đến chức năng của mạch máu nhằm dự đoán nguy cơ huyết áp cao nặng do bevacizumab. Sử dụng các mẫu huyết tương đã được xử lý từ 398 bệnh nhân được điều trị bằng bevacizumab trong hai thử nghiệm lâm sàng (CALGB 80303 và 90401), mức độ của 17 protein đã được đo thông qua phương pháp ELISA. Mối liên hệ giữa các protein và huyết áp cao cấp độ 3 do bevacizumab đã được thực hiện bằng cách tính toán tỷ lệ odds (OR) từ hồi quy logistic điều chỉnh theo độ tuổi, giới tính và thử nghiệm lâm sàng. Sử dụng điểm cắt tối ưu của từng protein, độ nhạy, độ đặc hiệu, giá trị dự đoán dương tính (PPV) và giá trị dự đoán âm tính (NPV) cho tình trạng huyết áp cao đã được ước tính. Năm protein cho thấy không có sự khác biệt về mức độ giữa các thử nghiệm lâm sàng và được sử dụng để phân tích. Mức độ thấp của angiopoietin-2 (p = 0.0013, OR 3.41, 95% CI 1.67-7.55), VEGF-A (p = 0.0008, OR 4.25, 95% CI 1.93-10.72), và VCAM-1 (p = 0.0067, OR 2.68, 95% CI 1.34-5.63) có liên quan đến tăng nguy cơ huyết áp cao cấp độ 3. Mô hình đa biến đề xuất các tác động độc lập của angiopoietin-2 (p = 0.0111, OR 2.71, 95% CI 1.29-6.10), VEGF-A (p = 0.0051, OR 3.66, 95% CI 1.54-9.73), và VCAM-1 (p = 0.0308, OR 2.27, 95% CI 1.10-4.92). Sự hiện diện của mức độ thấp của 2-3 protein có OR là 10.06 (95% CI 3.92-34.18, p = 1.80 × 10–5) cho nguy cơ huyết áp cao, với độ nhạy 89.7%, độ đặc hiệu 53.5%, PPV 17.3%, và NPV 97.9%. Đây là nghiên cứu đầu tiên cung cấp bằng chứng về các protein trong huyết tương có tiềm năng để dự đoán bệnh nhân có nguy cơ phát triển huyết áp cao do bevacizumab. Đăng ký thử nghiệm lâm sàng: ClinicalTrials.gov Identifier: NCT00088894 (CALGB 80303); và NCT00110214 (CALGB 90401).

Từ khóa

#huyết áp cao #bevacizumab #protein huyết tương #angiopoietin-2 #VEGF-A #VCAM-1 #dấu hiệu sinh học

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