Xét nghiệm dựa trên DNA methyl hóa để phát hiện ung thư thực quản

Biomarker Research - Tập 8 Số 1 - 2020
Sofia Salta1, Catarina Macedo‐Silva1, Vera Miranda-Gonçalves1, Nair Lopes1, Davide Gigliano1, Rita Guimarães1, Mónica Farinha1, Olga Sousa2, Rui Henrique3, Carmen Jerónimo4
1Cancer Biology & Epigenetics Group – Research Center, Portuguese Oncology Institute of Porto, Rua Dr António Bernardino de Almeida, 4200-072, Porto, Portugal
2Department of Radiation Oncology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino de Almeida, Porto, 4200-072, Portugal
3Department of Pathology, Portuguese Oncology Institute of Porto, Rua Dr. António Bernardino de Almeida, Porto, 4200-072, Portugal
4Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar– University of Porto , Rua de Jorge Viterbo Ferreira, 228, Porto, 4050-313, Portugal

Tóm tắt

Abstract Giới thiệu Ung thư thực quản (UCQ) là loại ung thư có tỷ lệ mắc đứng thứ 7 và là nguyên nhân hàng đầu thứ 6 gây tử vong liên quan đến ung thư. Hầu hết bệnh nhân được chẩn đoán ở giai đoạn bệnh tiến triển tại chỗ hoặc di căn, với tỷ lệ sống sót thấp. Cần thiết phải có các biomarker giúp phát hiện ung thư sớm để cải thiện quản lý bệnh nhân, hiệu quả điều trị và tỷ lệ sống sót. Trong bối cảnh này, các biomarker dựa trên epigenetics như DNA methyl hóa là những ứng cử viên tiềm năng. Phương pháp Trong nghiên cứu này, chúng tôi đã tìm cách xác định và kiểm định các biomarker dựa trên DNA methyl hóa nhằm phát hiện sớm và dự đoán phản ứng điều trị ở bệnh nhân UCQ. Mức độ methyl hóa promoter được đánh giá trong một loạt các mẫu UCQ chưa được điều trị, UCQ sau điều trị bổ trợ, và các mô thực quản bình thường, sử dụng phương pháp PCR định lượng đặc hiệu methyl hóa cho COL14A1, GPX3, và ZNF569. Kết quả Mức độ methyl hóa ZNF569 (ZNF569me) có sự khác biệt đáng kể giữa các mẫu UCQ và mẫu bình thường (p < 0.001). Hơn nữa, mức độ methyl hóa COL14A1 (COL14A1me) và methyl hóa GPX3 (GPX3me) phân biệt rõ ràng giữa các adenocarcinoma và carcinoma tế bào vảy so với các mẫu bình thường (p = 0.002 và p = 0.009, tương ứng). COL14A1me & ZNF569me xác định chính xác các adenocarcinoma (82.29%) trong khi GPX3me & ZNF569me xác định các carcinoma tế bào vảy với độ chính xác 81.73%. Hơn nữa, mức độ ZNF569meGPX3me có sự khác biệt đáng kể giữa các mẫu bình thường và các mẫu UCQ đã được điều trị trước. Kết luận Tiềm năng biomarker của một bảng gene methyl hóa cụ thể cho UCQ đã được xác thực. Những biomarker này có thể hữu ích cho việc phát hiện sớm và có thể cho phép xác định bệnh tồn dư tối thiểu sau điều trị bổ trợ.

Từ khóa


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