Dumitrescu Ramona G
Kelly Government Solutions, Bethesda, MD, USA.
Methods Mol Biol. 2018;1856:3-17. doi: 10.1007/978-1-4939-8751-1_1.
Over the last years, epigenetic changes, including DNA methylation and histone modifications detected in early tumorigenesis and cancer progression, have been proposed as biomarkers for cancer detection, tumor prognosis, and prediction to treatment response. Importantly for the clinical use of DNA methylation biomarkers, specific methylation signatures can be detected in many body fluids including serum/plasma samples. Several of these potential epigenetic biomarkers detected in women's cancers, colorectal cancers, prostate, pancreatic, gastric, and lung cancers are discussed. Studies conducted in breast cancer, for example, found that aberrant methylation detection of several genes in serum DNA and genome-wide epigenetic change could be used for early breast cancer diagnosis and prediction of breast cancer risk. In colorectal cancers, numerous studies have been conducted to identify specific methylation markers important for CRC detection and in fact clinical assays evaluating the methylation status of SEPT19 gene and vimentin, became commercially available. Furthermore, some epigenetic changes detected in gastric washes have been suggested as potential circulating noninvasive biomarkers for the early detection of gastric cancers. For the early detection of prostate cancer, few epigenetic markers have shown a better sensitivity and specificity than serum PSA, indicating that the inclusion of these markers together with current screening tools, could improve early diagnosis and may reduce unnecessary repeat biopsies. Similarly, in pancreatic cancers, abnormal DNA methylation of several genes including NPTX2, have been suggested as a diagnostic biomarker. Epigenetic dysregulation was also observed in several tumor suppressor genes and miRNAs in lung cancer patients, suggesting the important role of these changes in cancer initiation and progression. In conclusion, epigenetic changes detected in biological fluids could play an essential role in the early detection of several cancer types and this may have a great impact for the cancer precision medicine field.
在过去几年中，表观遗传变化，包括在肿瘤发生早期和癌症进展过程中检测到的DNA甲基化和组蛋白修饰，已被提议作为癌症检测、肿瘤预后和治疗反应预测的生物标志物。对于DNA甲基化生物标志物的临床应用而言，重要的是可以在包括血清/血浆样本在内的许多体液中检测到特定的甲基化特征。本文讨论了在女性癌症、结直肠癌、前列腺癌、胰腺癌、胃癌和肺癌中检测到的几种潜在表观遗传生物标志物。例如，在乳腺癌中进行的研究发现，血清DNA中几个基因的异常甲基化检测和全基因组表观遗传变化可用于早期乳腺癌诊断和乳腺癌风险预测。在结直肠癌中，已经进行了大量研究以确定对结直肠癌检测重要的特定甲基化标志物，事实上，评估SEPT19基因和波形蛋白甲基化状态的临床检测已商业化。此外，在胃灌洗液中检测到的一些表观遗传变化已被认为是早期检测胃癌的潜在循环无创生物标志物。对于前列腺癌的早期检测，很少有表观遗传标志物显示出比血清PSA更好的敏感性和特异性，这表明将这些标志物与当前的筛查工具结合使用，可以改善早期诊断并可能减少不必要的重复活检。同样，在胰腺癌中，包括NPTX2在内的几个基因的异常DNA甲基化已被提议作为诊断生物标志物。在肺癌患者的几个肿瘤抑制基因和miRNA中也观察到表观遗传失调，表明这些变化在癌症发生和进展中的重要作用。总之，在生物体液中检测到的表观遗传变化可能在几种癌症类型的早期检测中发挥重要作用，这可能对癌症精准医学领域产生重大影响。
