Potter Nicholas T, Hurban Patrick, White Mary N, Whitlock Kara D, Lofton-Day Catherine E, Tetzner Reimo, Koenig Thomas, Quigley Neil B, Weiss Gunter
Molecular Pathology Laboratory Network, Maryville TN;
EA | A Quintiles Company, Durham, NC;
Clin Chem. 2014 Sep;60(9):1183-91. doi: 10.1373/clinchem.2013.221044. Epub 2014 Jun 17.
Epi proColon® is a new blood-based colorectal cancer (CRC) screening test designed to determine the methylation status of a promoter region of the SEPT9 (septin 9) gene in cell-free DNA isolated from plasma. We describe the analytical and clinical performance of the test.
Analytical performance at 4 testing laboratories included determination of limit of detection, precision, and reproducibility of the SEPT9 test. Clinical performance was evaluated in a prospective study by use of samples (n = 1544) from subjects enrolled in the PRESEPT clinical trial. Results were analyzed by comparison with colonoscopy, the reference standard.
The limit of detection for methylated SEPT9 DNA was 7.8 pg/mL (95% CI 6-11 pg/mL) corresponding to <2 genome copies of methylated SEPT9 per milliliter of plasma. In the prospective clinical trial, sensitivity for all stages of CRC was 68% (95% CI 53%-80%) and for stage I-III CRC, 64% (48%-77%). Adjusted specificity, on the basis of negative colonoscopy findings, was 80.0% (78%-82%).
The Epi proColon test is a simple, real-time PCR-based assay for the detection of methylated SEPT9 DNA in blood that may provide a noninvasive CRC screening alternative for people noncompliant with current CRC screening guidelines.
Epi proColon®是一种新型的基于血液的结直肠癌（CRC）筛查检测方法，旨在测定从血浆中分离的游离DNA中SEPT9（septin 9）基因启动子区域的甲基化状态。我们描述了该检测方法的分析性能和临床性能。
4个检测实验室的分析性能包括测定SEPT9检测的检测限、精密度和重现性。通过使用来自PRESEPT临床试验受试者的样本（n = 1544）进行前瞻性研究来评估临床性能。通过与结肠镜检查（参考标准）进行比较来分析结果。
甲基化SEPT9 DNA的检测限为7.8 pg/mL（95%CI 6 - 11 pg/mL），相当于每毫升血浆中甲基化SEPT9的基因组拷贝数<2个。在前瞻性临床试验中，CRC各阶段的敏感性为68%（95%CI 53% - 80%），I - III期CRC的敏感性为64%（48% - 77%）。基于结肠镜检查阴性结果调整后的特异性为80.0%（78% - 82%）。
Epi proColon检测是一种基于实时PCR的简单检测方法，用于检测血液中甲基化的SEPT9 DNA，可为不符合当前CRC筛查指南的人群提供一种非侵入性的CRC筛查替代方法。
