5-Hydroxymethylome in Circulating Cell-free DNA as A Potential Biomarker for Non-small-cell Lung Cancer.

5-Hydroxymethylome in Circulating Cell-free DNA as A Potential Biomarker for Non-small-cell Lung Cancer.
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循环游离 DNA 中的 5-羟甲基化组作为非小细胞肺癌的潜在生物标志物

DOI:
10.1016/j.gpb.2018.06.002
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发表时间:
2018-06
期刊:
Genomics, proteomics & bioinformatics
影响因子:
--
通讯作者:
Tian X
Tian X
中科院分区:
其他
文献类型:
--
作者:
Zhang J;Han X;Gao C;Xing Y;Qi Z;Liu R;Wang Y;Zhang X;Yang YG;Li X;Sun B;Tian X

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非小细胞肺癌(NSCLC)是最常见的肺癌类型,占肺癌病例的85%,由于缺乏有效的早期诊断工具,诊断时往往已处于晚期。循环游离 DNA (cfDNA) 中携带癌症特异性表观遗传模式的 5-羟甲基胞嘧啶 (5hmC) 特征可能代表区分肿瘤和健康个体的有价值的生物标志物,因此可能对 NSCLC 诊断有用。在这里,我们采用灵敏可靠的方法对中国 NSCLC 患者 cfDNA 中的全基因组 5hmC 进行定位,并检测到与健康对照相比,肿瘤患者血液样本中基因体和启动子区域的 5hmC 显着增加。具体来说,我们使用基于机器学习的高精度肿瘤分类器从 66 名患者和 67 名健康对照中识别出 6 种潜在的生物标志物(平均降低准确度 >3.2,P<3.68E−19)。因此,我们的研究中鉴定出的肿瘤患者 cfDNA 中 5hmC 的独特特征可能为促进 NSCLC 新诊断和治疗方式的开发提供有价值的信息。
Non-small-cell lung cancer (NSCLC), the most common type of lung cancer accounting for 85% of the cases, is often diagnosed at advanced stages owing to the lack of efficient early diagnostic tools. 5-Hydroxymethylcytosine (5hmC) signatures in circulating cell-free DNA (cfDNA) that carries the cancer-specific epigenetic patterns may represent the valuable biomarkers for discriminating tumor and healthy individuals, and thus could be potentially useful for NSCLC diagnosis. Here, we employed a sensitive and reliable method to map genome-wide 5hmC in the cfDNA of Chinese NSCLC patients and detected a significant 5hmC gain in both the gene bodies and promoter regions in the blood samples from tumor patients compared with healthy controls. Specifically, we identified six potential biomarkers from 66 patients and 67 healthy controls (mean decrease accuracy >3.2, P < 3.68E−19) using machine-learning-based tumor classifiers with high accuracy. Thus, the unique signature of 5hmC in tumor patient’s cfDNA identified in our study may provide valuable information in facilitating the development of new diagnostic and therapeutic modalities for NSCLC.
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