Centre for Epidemiology and Biostatistics, The University of Melbourne, Melbourne, Victoria, Australia.
BMJ Open Gastroenterol. 2020 Feb 18;7(1):e000355. doi: 10.1136/bmjgast-2019-000355. eCollection 2020.
Circulating tumour DNA from colorectal cancer (CRC) is a biomarker for early detection of the disease and therefore potentially useful for screening. One such biomarker is the methylated SEPT9 (mSEPT9) gene, which occurs during CRC tumourigenesis. This systematic review and meta-analysis aims to establish the sensitivity, specificity and accuracy of mSEPT9 tests for the early diagnosis of CRC.
A systematic search of the relevant literature was conducted using Medline and Embase databases. Data were extracted from the eligible studies and analysed to estimate pooled sensitivity, specificity and diagnostic test accuracy.
Based on 19 studies, the pooled estimates (and 95% CIs) for mSEPT9 to detect CRC were: sensitivity 69% (62-75); specificity 92% (89-95); positive likelihood ratio 9.1 (6.1-13.8); negative likelihood ratio 0.34 (0.27-0.42); diagnostic OR 27 (15-48) and area under the curve 0.89 (0.86-0.91). The test has a positive predictive value of 2.6% and negative predictive value of 99.9% in an average risk population (0.3% CRC prevalence), and 9.5% (positive predictive value) and 99.6% (negative predictive value) in a high-risk population (1.2% CRC prevalence).
The mSEPT9 test has high specificity and moderate sensitivity for CRC and is therefore a potential alternative screening method for those declining faecal immunochemical test for occult blood (FIT) or other screening modalities. However, it is limited by its poor diagnostic performance for precancerous lesions (advanced adenomas and polyps) and its relatively high costs, and little is known about its acceptability to those declining to use the FIT.
结直肠癌（CRC）的循环肿瘤 DNA 是疾病早期检测的生物标志物，因此可能对筛查有用。其中一种生物标志物是甲基化 SEPT9（mSEPT9）基因，它发生在 CRC 肿瘤发生过程中。本系统评价和荟萃分析旨在确定 mSEPT9 检测用于 CRC 早期诊断的敏感性、特异性和准确性。
使用 Medline 和 Embase 数据库进行系统检索。从合格研究中提取数据并进行分析，以估计合并敏感性、特异性和诊断测试准确性。
基于 19 项研究，mSEPT9 检测 CRC 的合并估计值（95%CI）为：敏感性 69%（62-75）；特异性 92%（89-95）；阳性似然比 9.1（6.1-13.8）；阴性似然比 0.34（0.27-0.42）；诊断比值比 27（15-48）和曲线下面积 0.89（0.86-0.91）。在平均风险人群（CRC 患病率 0.3%）中，该检测的阳性预测值为 2.6%，阴性预测值为 99.9%，在高危人群（CRC 患病率 1.2%）中，阳性预测值为 9.5%，阴性预测值为 99.6%。
mSEPT9 检测对 CRC 具有高特异性和中等敏感性，因此可能是拒绝粪便免疫化学检测潜血（FIT）或其他筛查方法的人群的一种潜在替代筛查方法。然而，它受到对癌前病变（高级腺瘤和息肉）诊断性能差和相对较高成本的限制，并且对于那些拒绝使用 FIT 的人来说，其可接受性知之甚少。
