Feasibility of methylatedctDNAdetection in plasma samples of oropharyngeal squamous cell carcinoma patients
Feasibility of methylatedctDNAdetection in plasma samples of oropharyngeal squamous cell carcinoma patients
复制标题
DOI：
10.1002/hed.26385
复制
发表时间：
2020-07-20
影响因子：
2.9
通讯作者：
de Carvalho, Ana Carolina
中科院分区：
文献类型：
--
作者：
de Jesus, Lais Machado;dos Reis, Mariana Bisarro;de Carvalho, Ana Carolina
背景口咽鳞状细胞癌(OpSCCs)常伴有较高的治疗失败率。目的评价OPSCC患者血浆甲基化标志物作为准确/非侵入性随访的新工具。方法对52例福尔马林固定石蜡包埋组织(FFPE)和15例配对血浆(n=15)进行CCNA1、DAPK、CDH8和TIMP3甲基化检测。结果71%(37/52)的活检组织中至少有一个评估基因发生甲基化，肿瘤或CCNA1甲基化与无复发生存率相关。11/15(73.3%)的血浆标本中检出甲基化的循环肿瘤DNA(meth-ctDNA)，而健康对照组的血浆标本均为阴性(曲线下面积=0.867；95%可信区间=0.720~1.000)。此外，在随访期间收集的血浆中甲基硫代脱氧核糖核酸的初步检测结果与患者的预后非常吻合。结论应用ddPCR检测血浆中的meth-ctDNA是可行的，经进一步验证后有可能应用于常规检测。
Background Oropharyngeal squamous cell carcinomas (OpSCCs) are commonly associated with high rates of treatment failure. Objectives To evaluate methylation-based markers in plasma from OpSCC patients as emerging tools for accurate/noninvasive follow-up. Methods Pretreatment formalin-fixed paraffin-embedded (FFPE) biopsies (n = 52) and paired plasma (n = 15) were tested for the methylation ofCCNA1,DAPK,CDH8, andTIMP3by droplet digital PCR (ddPCR). Results Seventy-one percent (37/52) of the biopsies showed methylation of at least one of the evaluated genes and tumorCCNA1methylation was associated with recurrence-free survival. Methylated circulating tumor DNA (meth-ctDNA) was detected in 11/15 (73.3%) plasma samples; conversely, plasma samples from healthy controls were all negative for DNA methylation (area under the curve = 0.867; 95% confidence interval = 0.720-1.000). Additionally, preliminary results on the detection of meth-ctDNA in plasma collected during follow-up closely matched patient outcome. Conclusions The results suggest the feasibility of detecting meth-ctDNA in plasma using ddPCR and a possible application on routine setting after further validation.