Kim Chang Woo, Kim Hyunjin, Kim Hyoung Rae, Kye Bong-Hyeon, Kim Hyung Jin, Min Byung Soh, Oh Tae Jeong, An Sungwhan, Lee Suk-Hwan
Department of Surgery, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, 892 Dongnam-ro, Seoul, Gangdong-gu, 05278, Korea.
Department of Surgery, Koo Hospital, 141 Gamsambuk-gil, Daegu, Korea.
BMC Gastroenterol. 2021 Apr 15;21(1):173. doi: 10.1186/s12876-021-01759-9.
Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required.
All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer's protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer's instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. C values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases).
This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC.
This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1 .
结直肠癌（CRC）的预防和早期检测是全球重点关注的问题，许多国家都在开展基于人群的CRC筛查项目。尽管结肠镜检查是早期CRC检测最准确的诊断方法，但由于其侵入性和需要进行大量肠道准备，其依从性仍然较低。非侵入性的粪便潜血试验或粪便免疫化学试验也可采用；然而，它们的灵敏度相对较低。Syndecan-2（SDC2）是一种用于CRC早期检测的基于粪便的DNA甲基化标志物。使用EarlyTect™-结肠癌检测方法，先前已证明粪便DNA中SDC2甲基化检测CRC的灵敏度和特异性均大于90%。因此，现在需要进行一项更大规模的试验来验证其在无症状人群中用于CRC筛查的效果。
所有参与者在接受筛查结肠镜检查前均需采集粪便（至少20克）。样本将被送往中心实验室进行分析。粪便DNA将使用GT粪便DNA提取试剂盒，按照制造商的方案进行分离。在进行甲基化检测前，粪便DNA（每个反应2微克）将按照制造商的说明用亚硫酸氢盐处理。SDC2和COL2A1对照反应将在同一管中进行。SDC2甲基化检测将使用AB 7500快速实时PCR系统进行。C值将使用该仪器附带的7500软件进行计算。EarlyTect™-结肠癌检测的结果将与结肠镜检查以及任何来自具有临床意义的活检或随后切除病变的相应诊断组织病理学结果进行比较。根据这些结果，参与者将被分为三组：CRC组、息肉组和阴性组。将为参与者记录以下临床数据：性别、年龄、结肠镜检查结果和临床分期（针对CRC病例）。
本试验研究了一种能够在无症状人群的人类粪便DNA中定量检测单一DNA标志物SDC2甲基化的设备的临床性能。预计该试验结果将对CRC筛查有益，并可能有助于使结肠镜检查成为仅用于CRC高风险人群的选择性检查。
本试验（NCT04304131）于2020年3月11日在ClinicalTrials.gov注册，可在https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1查询。
