Combination of RERG and ZNF671 methylation rates in circulating cell-free DNA: A novel biomarker for screening of nasopharyngeal carcinoma
Combination of RERG and ZNF671 methylation rates in circulating cell-free DNA: A novel biomarker for screening of nasopharyngeal carcinoma
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循环游离 DNA 中 RERG 和 ZNF671 甲基化率的组合：用于筛查鼻咽癌的新型生物标志物
DOI：
10.1111/cas.14431
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发表时间：
2020-05-19
期刊：
影响因子：
5.7
通讯作者：
Murata, Mariko
中科院分区：
文献类型：
--
作者：
Xu, Yifei;Zhao, Weilin;Murata, Mariko
鼻咽癌（NPC）是东南亚地区的一种常见恶性肿瘤，因此，鉴定用于NPC筛查的易于检测的生物标志物对于更好的诊断和预后至关重要。使用基于下一代测序方法的全基因组和靶向分析，我们先前表明基因启动子在NPC组织中高度甲基化。为了证实基因DNA甲基化率是否可以作为鼻咽癌筛查的生物标志物，招募了79例组织学诊断的鼻咽癌患者和29例非癌症患者。使用实时PCR（qAMP）进行DNA甲基化的方便定量分析，包括用甲基化敏感性和/或甲基化依赖性限制性酶预处理组织DNA和来自非溶血性血浆的循环无细胞DNA（ccfDNA）。qAMP分析显示，RERG、ZNF 671、ITGA 4和SHISA 3的甲基化率在NPC原发性肿瘤组织中显著高于非癌组织，具有足够的受试者工作特征曲线下面积（AUC）诊断准确性。有趣的是，ccfDNA中较高的RERG甲基化率具有统计学显著性，并产生了非常好的AUC;然而，ZNF 671、ITGA 4和SHISA 3的甲基化率并不显著。此外，ccfDNA中RERG和ZNF 671甲基化率的组合显示出比它们中的任何一个单独更高的诊断准确性。结论：ccfDNA中特异性基因甲基化率可作为鼻咽癌早期检测和筛查的新生物标志物。
Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia, hence, identifying easily detectable biomarkers for NPC screening is essential for better diagnosis and prognosis. Using genome-wide and targeted analyses based on next-generation sequencing approaches, we previously showed that gene promoters are hypermethylated in NPC tissues. To confirm whether DNA methylation rates of genes could be used as biomarkers for NPC screening, 79 histologically diagnosed NPC patients and 29 noncancer patients were recruited. A convenient quantitative analysis of DNA methylation using real-time PCR (qAMP) was carried out, involving pretreatment of tissue DNA, and circulating cell-free DNA (ccfDNA) from nonhemolytic plasma, with methylation-sensitive and/or methylation-dependent restriction enzymes. The qAMP analyses revealed that methylation rates of RERG, ZNF671, ITGA4, and SHISA3 were significantly higher in NPC primary tumor tissues compared to noncancerous tissues, with sufficient diagnostic accuracy of the area under receiver operating characteristic curves (AUC). Interestingly, higher methylation rates of RERG in ccfDNA were statistically significant and yielded a very good AUC; however, those of ZNF671, ITGA4, and SHISA3 were not significant. Furthermore, the combination of methylation rates of RERG and ZNF671 in ccfDNA showed higher diagnostic accuracy than either of them individually. In conclusion, the methylation rates of specific genes in ccfDNA can serve as novel biomarkers for early detection and screening of NPC.