研究动态
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IMPRESS:使用限制性内切酶和 smMIP 测序改进甲基化分析,并结合新的生物标志物组,创建多癌症检测分析。

IMPRESS: Improved methylation profiling using restriction enzymes and smMIP sequencing, combined with a new biomarker panel, creating a multi-cancer detection assay.

发表日期:2024 Aug 24
作者: Janah Vandenhoeck, Isabelle Neefs, Thomas Vanpoucke, Joe Ibrahim, Arvid Suls, Dieter Peeters, Anne Schepers, Alexander Hoischen, Erik Fransen, Marc Peeters, Guy Van Camp, Ken Op de Beeck
来源: BRITISH JOURNAL OF CANCER

摘要:

尽管癌症诊断在世界范围内取得了进展,但仍需要更灵敏的诊断生物标志物。甲基化组在过去几十年中得到了广泛的研究,但仍然缺乏一种低成本、无亚硫酸氢盐的多重分析检测方法。我们开发了一种名为 IMPRESS 的甲基化检测技术,该技术结合了甲基化敏感的限制性酶和单分子分子标记技术。倒置探头。我们利用这项技术开发了针对全球八种最致命癌症类型的多种癌症检测方法。我们选择了 1791 个 CpG 位点,可以根据 DNA 甲基化区分肿瘤和正常组织。使用 IMPRESS 对 35 个血液样本、111 个肿瘤样本和 114 个正常样本中的这些位点进行了分析。最后,建立了分类器模型。我们介绍了IMPRESS的成功开发,并用ddPCR对其进行了验证。最终的区分肿瘤和正常样本的分类器模型由 358 个 CpG 靶位点构建,灵敏度达到 0.95,特异性达到 0.91。此外,我们提供的数据凸显了 IMPRESS 在液体活检方面的潜力。我们成功创建了一种创新的 DNA 甲基化检测技术。通过将此方法与新的多癌症生物标志物组合相结合,我们开发了一种敏感且特异的多癌症检测方法,可用于液体活检。© 2024。作者。
Despite the worldwide progress in cancer diagnostics, more sensitive diagnostic biomarkers are needed. The methylome has been extensively investigated in the last decades, but a low-cost, bisulfite-free detection method for multiplex analysis is still lacking.We developed a methylation detection technique called IMPRESS, which combines methylation-sensitive restriction enzymes and single-molecule Molecular Inversion Probes. We used this technique for the development of a multi-cancer detection assay for eight of the most lethal cancer types worldwide. We selected 1791 CpG sites that can distinguish tumor from normal tissue based on DNA methylation. These sites were analysed with IMPRESS in 35 blood, 111 tumor and 114 normal samples. Finally, a classifier model was built.We present the successful development of IMPRESS and validated it with ddPCR. The final classifier model discriminating tumor from normal samples was built with 358 CpG target sites and reached a sensitivity of 0.95 and a specificity of 0.91. Moreover, we provide data that highlight IMPRESS's potential for liquid biopsies.We successfully created an innovative DNA methylation detection technique. By combining this method with a new multi-cancer biomarker panel, we developed a sensitive and specific multi-cancer assay, with potential use in liquid biopsies.© 2024. The Author(s).