Dollinger Matthias M, Behl Susanna, Fleig Wolfgang E
Clin Lab. 2018 Oct 1;64(10):1719-1730. doi: 10.7754/Clin.Lab.2018.180521.
Although colonoscopy-based screening has proven to be highly effective in detecting colorectal cancer (CRC), participation rates remain disappointing. Development of CRC is associated with a number of genetic or somatic mutations. New, non-invasive stool tests are currently being developed based on the detection of these alterations. We investigated if a non-invasive stool assay can offer sufficient sensitivity and specificity to supplement colonoscopy-based screening.
We compared a combined stool assay, which incorporates fecal occult blood testing (FOBT), quantification of human DNA (hDNA) as well as detection of genetic mutations of KRAS and BRAF (Combined DNA stool assay), with commercially available FOBT and M2-PK tests in a multi-centric six-armed pre-clinical case cohort study. Seven hundred thirty-four patients were recruited prior to elective/screening colonoscopy or prior to surgery in case of a recent CRC diagnosis. According to clinical assessment and colonoscopy/histology results, the following groups were assigned: controls, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), hyperplastic polyps, adenomas, and CRC. Finally, 566 out of 734 patients (77.1%) were screened for CRC and overall gut status via colonoscopy, FOBT, M2-PK, with combined FOBT/M2-PK and the Combined DNA stool assay as described here.
All sensitivities and specificities are measured against histologically confirmed results by colonoscopy. Confirmed sensitivities for detecting colorectal cancer were 68% with FOBT, 83% with M2-PK, 90% with combined FOBT and M2-PK, and 85% with the Combined DNA stool assay. Specificities were 96% with FOBT, 61% with M2-PK, 62% with combined FOBT and M2-PK, and 92% with the Combined DNA stool assay in the control group with no pathological findings during colonoscopy.
The Combined DNA stool assay detects CRC with a significantly higher Youden Index than the other reviewed non-invasive screening options. The results also suggest that the Combined DNA stool assay represents a reliable assay for detecting colorectal cancer, sufficient to be recommended as a supplement to colonoscopy screening.
尽管基于结肠镜检查的筛查已被证明在检测结直肠癌（CRC）方面非常有效，但参与率仍然令人失望。结直肠癌的发生与许多基因或体细胞突变有关。目前正在基于对这些改变的检测开发新的非侵入性粪便检测方法。我们研究了一种非侵入性粪便检测方法是否能提供足够的敏感性和特异性来补充基于结肠镜检查的筛查。
在一项多中心六臂临床前病例队列研究中，我们将一种联合粪便检测方法（结合粪便潜血试验（FOBT）、人DNA（hDNA）定量以及KRAS和BRAF基因突变检测（联合DNA粪便检测））与市售的FOBT和M2-PK检测进行了比较。在择期/筛查结肠镜检查前或近期诊断为CRC的情况下，在手术前招募了734名患者。根据临床评估和结肠镜检查/组织学结果，分为以下几组：对照组、肠易激综合征（IBS）、炎症性肠病（IBD）、增生性息肉、腺瘤和CRC。最后，对734名患者中的566名（77.1%）进行了CRC和整体肠道状况的筛查，方法包括结肠镜检查、FOBT、M2-PK、联合FOBT/M2-PK以及本文所述的联合DNA粪便检测。
所有敏感性和特异性均根据结肠镜检查组织学确诊结果进行测量。检测结直肠癌的确诊敏感性为：FOBT为68%，M2-PK为83%，联合FOBT和M2-PK为90%，联合DNA粪便检测为85%。在结肠镜检查无病理发现的对照组中，特异性分别为：FOBT为96%，M2-PK为61%，联合FOBT和M2-PK为62%，联合DNA粪便检测为92%。
联合DNA粪便检测在检测CRC时的约登指数显著高于其他经审查的非侵入性筛查方法。结果还表明，联合DNA粪便检测是一种检测结直肠癌的可靠检测方法，足以推荐作为结肠镜检查筛查的补充。
