Institute for Biomedical Engineering, Science and Technology (I BEST), Partnership between Toronto Metropolitan University and St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada.
Ultrashort Laser Nanomanufacturing Research Facility, Faculty of Engineering and Architectural Sciences, Toronto Metropolitan University, 350 Victoria Street, Toronto, Ontario M5B 2K3, Canada.
Nano Lett. 2023 May 24;23(10):4142-4151. doi: 10.1021/acs.nanolett.2c04914. Epub 2023 May 3.
Natural killer (NK) cells undergo multiple DNA genomic alterations, especially methylation-based modifications that affect activation and function. Several epigenetic modifier markers have been targeted for immunotherapy to date, but the possibility of cancer diagnosis using NK cell's DNA has been overlooked. Here, we investigated the potential use of NK cell DNA genome modifications as markers for the diagnosis of colorectal cancer (CRC) and validated their efficacy in CRC patients. Using Raman spectroscopy as the detection methodology, we identified CRC-specific methylation signatures by comparing CRC-interacted NK cells to healthy circulating NK cells. Subsequently, we identified methylation-dependent alterations in these NK cell populations. These markers were then utilized by a machine learning algorithm to develop a diagnostic model with predictive capabilities. The diagnostic prediction model accurately differentiated CRC patients from normal controls. Our findings demonstrated the utility of NK DNA markers in the diagnosis of CRC.
自然杀伤 (NK) 细胞经历多种 DNA 基因组改变，特别是影响激活和功能的基于甲基化的修饰。迄今为止，已经针对几种表观遗传修饰标志物进行了免疫治疗，但使用 NK 细胞 DNA 进行癌症诊断的可能性被忽视了。在这里，我们研究了 NK 细胞 DNA 基因组修饰作为结直肠癌 (CRC) 诊断标志物的潜力，并在 CRC 患者中验证了其疗效。使用拉曼光谱作为检测方法，我们通过比较与 CRC 相互作用的 NK 细胞与健康循环 NK 细胞，确定了 CRC 特异性甲基化特征。随后，我们确定了这些 NK 细胞群体中依赖于甲基化的改变。然后，机器学习算法利用这些标记物开发了具有预测能力的诊断模型。该诊断预测模型能够准确地区分 CRC 患者和正常对照者。我们的研究结果表明，NK DNA 标志物在 CRC 的诊断中有一定的应用价值。
