Department of Medicine II, Klinikum rechts der Isar, Technische Universität, München, Germany.
PLoS One. 2010 Feb 4;5(2):e9061. doi: 10.1371/journal.pone.0009061.
Screening for colorectal cancer (CRC) has shown to reduce cancer-related mortality, however, acceptance and compliance to current programmes are poor. Developing new, more acceptable non-invasive tests for the detection of cancerous and precancerous colorectal lesions would not only allow preselection of individuals for colonoscopy, but may also prevent cancer by removal of precancerous lesions.
Plasma from 128 individuals (cohort I - exploratory study: 73 cases / 55 controls) was used to test the performance of a single marker, SEPT9, using a real-time quantitative PCR assay. To validate performance of SEPT9, plasma of 76 individuals (cohort II - validation study: 54 cases / 22 controls) was assessed. Additionally, improvement of predictive capability considering SEPT9 and additionally ALX4 methylation was investigated within these patients.
In both cohorts combined, methylation of SEPT9 was observed in 9% of controls (3/33), 29% of patients with colorectal precancerous lesions (27/94) and 73% of colorectal cancer patients (24/33). The presence of both SEPT9 and ALX4 markers was analysed in cohort II and was observed in 5% of controls (1/22) and 37% of patients with polyps (18/49). Interestingly, also 3/5 (60%) patients with colorectal cancer were tested positive by the two marker panel in plasma.
While these data confirm the detection rate of SEPT9 as a biomarker for colorectal cancer, they also show that methylated DNA from advanced precancerous colorectal lesions can be detected using a panel of two DNA methylation markers, ALX4 and SEPT9. If confirmed in larger studies these data indicate that screening for colorectal precancerous lesions with a blood-based test may be as feasible as screening for invasive cancer.
结直肠癌（CRC）的筛查已被证明可降低癌症相关死亡率，但目前的筛查计划接受度和依从性都很差。开发新的、更易接受的非侵入性检测方法来检测癌性和癌前结直肠病变，不仅可以对个体进行结肠镜检查前的筛选，还可以通过切除癌前病变来预防癌症。
使用实时定量 PCR 检测方法，对来自 128 名个体（队列 I-探索性研究：73 例病例/55 例对照）的血浆进行了一种单一标志物 SEPT9 的性能测试。为了验证 SEPT9 的性能，评估了来自 76 名个体（队列 II-验证性研究：54 例病例/22 例对照）的血浆。此外，还在这些患者中研究了考虑 SEPT9 和另外的 ALX4 甲基化后，对预测能力的改善。
在两个队列的综合分析中，在 33 名对照者中有 9%（3/33），94 名结直肠癌前病变患者中有 29%（27/94），33 名结直肠癌患者中有 73%（24/33）观察到 SEPT9 的甲基化。在队列 II 中分析了 SEPT9 和 ALX4 两个标志物的存在情况，在 22 名对照者中有 5%（1/22），在 49 名息肉患者中有 37%（18/49）观察到。有趣的是，在血浆中，5 名结直肠癌患者中有 3 名（60%）也通过了两个标志物面板的检测。
虽然这些数据证实了 SEPT9 作为结直肠癌生物标志物的检测率，但它们也表明，使用两种 DNA 甲基化标志物（ALX4 和 SEPT9）可以检测到晚期结直肠癌前病变的甲基化 DNA。如果在更大的研究中得到证实，这些数据表明，使用基于血液的检测方法筛查结直肠癌前病变可能与筛查侵袭性癌症一样可行。
