Brito-Rocha Tiago, Constâncio Vera, Leite-Silva Pedro, Carvalho-Maia Carina, Sequeira José Pedro, Salta Sofia, Lobo João, Machado Diana Inês, Nunes Sandra P, Silva-Santos Rui, Freitas Rui, Gonçalves Dias Carlos, Vieira Cláudia, Soares Marta, Henrique Rui, Jerónimo Carmen
Cancer Biology and Epigenetics Group, Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Porto, Portugal.
Doctoral Program in Biomedical Sciences, ICBAS-School of Medicine & Biomedical Sciences, University of Porto, Porto, Portugal.
Int J Cancer. 2025 Sep 1;157(5):1006-1019. doi: 10.1002/ijc.35467. Epub 2025 May 2.
Early cancer detection through minimally invasive methods is key for improving patient outcomes. We aimed to assess the performance of a novel blood-based test leveraging DNA methylation patterns for simultaneous detection of lung (LC), breast (BrC), colorectal (CRC), and prostate (PCa) cancer. Using The Cancer Genome Atlas (TCGA) methylation data, we identified shared hypermethylated gene promoters (ADCY4, MIR129-2, NID2, and MAGI2) among those four cancers. Validation was performed using online datasets, an in-house tissue set (N = 179), and plasma samples (N = 485) using droplet digital PCR (ddPCR). The test showed sensitivities of 81.82% (lung), 45% (breast), 69.23% (colorectal), and 44.14% (prostate), with 91.04% specificity. Overall, the PanCancer panel achieved 60.1% sensitivity and 87.4% specificity in detecting these four cancers. In early-stage cancers, sensitivities were slightly lower but followed a similar trend. Additionally, the test detected nine other cancer types in plasma. This proof-of-concept study demonstrates the feasibility of a single methylation-targeted blood test for multi-cancer detection, offering potential as an affordable and scalable screening tool for early cancer detection.
通过微创方法进行早期癌症检测是改善患者预后的关键。我们旨在评估一种利用DNA甲基化模式同时检测肺癌（LC）、乳腺癌（BrC）、结直肠癌（CRC）和前列腺癌（PCa）的新型血液检测方法的性能。利用癌症基因组图谱（TCGA）甲基化数据，我们在这四种癌症中确定了共同的高甲基化基因启动子（ADCY4、MIR129-2、NID2和MAGI2）。使用在线数据集、内部组织样本集（N = 179）和血浆样本（N = 485），通过液滴数字PCR（ddPCR）进行验证。该检测方法在肺癌中的灵敏度为81.82%，乳腺癌为45%，结直肠癌为69.23%，前列腺癌为44.14%，特异性为91.04%。总体而言，泛癌检测面板在检测这四种癌症时的灵敏度为60.1%，特异性为87.4%。在早期癌症中，灵敏度略低，但趋势相似。此外，该检测还在血浆中检测到了其他九种癌症类型。这项概念验证研究证明了单一甲基化靶向血液检测用于多癌检测的可行性，并有望成为一种经济实惠且可扩展的早期癌症检测筛查工具。
