结直肠癌筛查人群血浆游离DNA浓度及其对甲基化筛检技术的影响  

The impact of plasma cell-free DNA concentration in colorectal cancer screening population on methylation screening techniques

作　　者：郑卫方 柴晓银 潘富珍 徐美慧 章喆 蓝柳豪 黄彦钦[3] 郑树[3] Zheng Weifang

机构地区：[1]浙江省兰溪市中医院,321100 [2]浙江省兰溪市红十字医院,321100 [3]浙江大学医学院附属第二医院肿瘤研究所(教育部恶性肿瘤预警与干预重点实验室),310013

出　　处：《浙江临床医学》2023年第10期1438-1441,1444,共5页Zhejiang Clinical Medical Journal

基　　金：浙江省金华市科学技术项目(2020-63)。

摘　　要：目的明确结直肠癌筛查人群血浆中游离DNA(cfDNA)浓度的特点,试验cfDNA定量能否提高血浆甲基化标志物筛查结直肠癌的性能。方法一项基于人群研究从社区招募40~74岁个体。结肠镜检查前进行问卷调查和抽血,纯化血浆cfDNA进行浓度测定,然后用MethyLight检测两种甲基化标志物(SEPT9和C9ORF50)。构建加或不加cfDNA浓度因素的多因素风险预测模型,生成接收操作曲线,比较诊断性能。结果最终纳入479例,其中进展期肿瘤58例。血浆cfDNA浓度最高的前10位个体平均(139.96±183.10),cfDNA浓度是其余个体(7.82±4.42)的18倍。cfDNA浓度升高者特征多样,仅与腹痛、高脂血症统计学相关。加或不加血浆cfDNA浓度的风险模型预测进展期肿瘤无显著差异(AUC=0.579和0.591,P=0.466)。对样本设置cfDNA浓度阳性阈值后,甲基化检测对进展期肿瘤敏感性(19.0%,95%CI:8.9~29.1)和特异性(89.1%,95%CI:86.1~92.1)并未提高。结论社区人群中少数看似正常的个体,由于未知原因,其血浆中cfDNA浓度较高。血浆cfDNA定量可能无助于大肠癌筛查。Objective To investigate the characteristics of plasma cell-free DNA concentration in colorectal cancer screening population and to determine whether the quantity of cfDNA can improve the performance of plasma methylation markers for screening for colorectal cancer.Methods A population-based study recruited individuals aged from 40 to 74 years from the community.Questionnaire survey and blood sampling were carried out before colonoscopy.The concentration of purified plasma cfDNA was determined,and then two methylation markers(SEPT9 and C9ORF50)were detected by MethyLight.Constructed a multi-factor risk prediction model with or without cfDNA concentration.Generated a receive operation curve.The diagnostic performance of screening test with and without cfDNA concentration cutoff value was compared.Results 479 patients were included,including 58 patients with advanced tumor.In the first 10 people,the average cfDNA concentration per milliliter of plasma(139.96±183.10)was 18 times higher than that of the other individuals.The characteristics of elevated cfDNA concentration were diverse and only associated with abdominal pain and hyperlipidemia.The risk model with or without plasma cfDNA concentrations predicted no significant difference in advanced tumors(AUC=0.579 and 0.591,P=0.466).After the positive threshold of cfDNA concentration was set on the sample,the sensitivity of methylation test to advanced tumor(19.0%,95%CI:8.9~29.1)and specificity(89.1%,95%CI:86.1~92.1)did not improve.Conclusion A small number of seemingly normal individuals in the community have higher plasma cfDNA levels due to unknown reasons.The quantification of plasma cfDNA may not be helpful for the screening of colorectal cancer.

关 键 词：结直肠肿瘤 血浆游离DNA 甲基化 

分 类 号：R735.34[医药卫生—肿瘤]