新型粪便 DNA 甲基化 SDC2 检测用于结直肠癌检测的稳健性能：一项多中心临床研究。

Robust performance of a novel stool DNA test of methylated SDC2 for colorectal cancer detection: a multicenter clinical study.

机构信息

Department of Colorectal Surgery, Guangdong Institute of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, , Sun Yat-Sen University, Yuancun Erheng Road, Guangzhou, 510655, Guangdong, China.

Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou, Guangdong, China.

出版信息

Clin Epigenetics. 2020 Oct 30;12(1):162. doi: 10.1186/s13148-020-00954-x.

DOI:10.1186/s13148-020-00954-x

PMID:33126908

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7602331/

Abstract

BACKGROUND AND AIMS

Stool DNA testing is an emerging and attractive option for colorectal cancer (CRC) screening. We previously evaluated the feasibility of a stool DNA (sDNA) test of methylated SDC2 for CRC detection. The aim of this study was to assess its performance in a multicenter clinical trial setting.

METHODS

Each participant was required to undergo a sDNA test and a reference colonoscopy. The sDNA test consists of quantitative assessment of methylation status of SDC2 promoter. Results of real-time quantitative methylation-specific PCR were dichotomized as positive and negative, and the main evaluation indexes were sensitivity, specificity, and kappa value. All sDNA tests were performed and analyzed independently of colonoscopy.

RESULTS

Among the 1110 participants from three clinical sites analyzed, 359 and 38 were diagnosed, respectively, with CRC and advanced adenomas by colonoscopy. The sensitivity of the sDNA test was 301/359 (83.8%) for CRC, 16/38 (42.1%) for advanced adenomas, and 134/154 (87.0%) for early stage CRC (stage I-II). Detection rate did not vary significantly according to age, tumor location, differentiation, and TNM stage, except for gender. The follow-up testing of 40 postoperative patients with CRC returned negative results as their tumors had been surgically removed. The specificity of the sDNA test was 699/713 (98.0%), and unrelated cancers and diseases did not seem to interfere with the testing. The kappa value was 0.84, implying an excellent diagnostic consistency between the sDNA test and colonoscopy.

CONCLUSION

Noninvasive sDNA test using methylated SDC2 as the exclusive biomarker is a clinically viable and accurate CRC detection method.

CHINESE CLINICAL TRIAL REGISTRY

Chi-CTR-TRC-1900026409, retrospectively registered on October 8, 2019; http://www.chictr.org.cn/edit.aspx?pid=43888&htm=4 .

摘要

背景与目的

粪便 DNA 检测是一种新兴的、有吸引力的结直肠癌（CRC）筛查方法。我们之前评估了甲基化 SDC2 粪便 DNA（sDNA）检测用于 CRC 检测的可行性。本研究的目的是在多中心临床试验环境中评估其性能。

方法

每位参与者均需进行 sDNA 检测和参考结肠镜检查。sDNA 检测包括 SDC2 启动子甲基化状态的定量评估。实时定量甲基化特异性 PCR 的结果被分为阳性和阴性，并将灵敏度、特异性和kappa 值作为主要评价指标。所有 sDNA 检测均在不依赖结肠镜检查的情况下独立进行和分析。

结果

在三个临床中心的 1110 名参与者中，359 人经结肠镜检查诊断为 CRC，38 人诊断为高级腺瘤。sDNA 检测对 CRC 的灵敏度为 301/359（83.8%），对高级腺瘤的灵敏度为 16/38（42.1%），对早期 CRC（I-II 期）的灵敏度为 134/154（87.0%）。检测率与年龄、肿瘤位置、分化和 TNM 分期无关，但与性别有关。40 例术后 CRC 患者的随访检测结果均为阴性，因为他们的肿瘤已被手术切除。sDNA 检测的特异性为 699/713（98.0%），且无关的癌症和疾病似乎不会干扰检测。kappa 值为 0.84，表明 sDNA 检测与结肠镜检查之间具有极好的诊断一致性。