A simplified, non-invasive fecal-based DNA integrity assay and iFOBT for colorectal cancer detection
A simplified, non-invasive fecal-based DNA integrity assay and iFOBT for colorectal cancer detection
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DOI：
10.1007/s00384-010-1128-x
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发表时间：
2011-05-01
影响因子：
2.8
通讯作者：
Bernardini, Sergio
中科院分区：
文献类型：
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作者：
Kalimutho, Murugan;Blanco, Giovanna Del Vecchio;Bernardini, Sergio
从结直肠上皮脱落的肿瘤细胞具有功能失调的凋亡机制，因此有可能在粪便中鉴定高分子量DNA片段。为评价粪便DNA完整性检测与免疫学粪便潜血试验（iFOBT）和钙卫蛋白检测在结直肠癌（CRC）和腺瘤诊断中的敏感性和特异性，本研究采用前瞻性单中心研究方法，收集204例受试者粪便标本，采用定量变性高效液相色谱法（QdHPLC）检测DNA完整性。使用商业试剂盒评估钙卫蛋白和iFOBT。采用受试者工作特征（ROC）曲线分析方法对192份粪便标本进行检测，12份因DNA降解而被排除。我们发现粪便中长DNA（L-DNA）的出现，CRC检测的敏感性为86%（n = 24/28），特异性为81%。为了最小化开发的测试的假阳性病例，评估ROC曲线下面积，使得特异性增加至92%，灵敏度降低至79%，p = 0.0001，用于CRC检测。iFOBT阳性率为51%（n = 14/27），而钙卫蛋白阳性率为75%（n = 18/27）。iFOBT和L-DNA的组合识别了更多数量的CRC病例，灵敏度为89%，特异性为95%，p < 0.001。该组合还提高了息肉的敏感性，特别是高度异型增生和晚期腺瘤（33%，p = 0.0015），而不是一个单一的评价测定（17-21%）。这项研究说明了粪便DNA完整性测定的有用性，通过QdHPLC作为一种非侵入性的，易于执行，并可重复的方法，在检测个体与结肠直肠瘤形成的高灵敏度。iFOBT和L-DNA的组合提高了CRC和腺瘤检测的灵敏度。
Neoplasia cells exfoliated from colorectal epithelium have dysfunctional apoptotic mechanisms, thus it is possible to identify high-molecular weight DNA fragments in feces. This prospective single-center study was performed to evaluate the sensitivity and specificity of fecal-based DNA integrity versus immunological fecal occult blood test (iFOBT) and calprotectin for colorectal cancer (CRC) and adenoma detection.Feces were collected from 204 subjects and DNA integrity was quantified by quantitative-denaturing high performance liquid chromatography (QdHPLC). Calprotectin and iFOBT were assessed using commercial kits. The diagnostic performance was calculated by receiver operating characteristic (ROC) curves analysis.A total of 192 fecal specimens were analyzed and 12 samples were excluded due to DNA degradation. We found long DNA (L-DNA) occurrence in feces with a sensitivity of 86% (n = 24/28) and a specificity of 81% for CRC detection. To minimize false-positive cases of the developed test, area under the curve of ROC was evaluated such that the specificity was increased to 92% with decreased sensitivity to 79%, p = 0.0001 for CRC detection. iFOBT was positive in 51% (n = 14/27) while calprotectin was positive in 75% (n = 18/27). The combination of iFOBT and L-DNA identified a greater number of CRC cases with a sensitivity of 89% and a specificity of 95%, p < 0.001. The combination also improved the sensitivity of polyps, particularly high-grade dysplasia and advanced adenoma (33%, p = 0.0015) as opposed to a single evaluation assay (17-21%).This study illustrates the usefulness of fecal DNA integrity assay by QdHPLC as a non-invasive, easy-to-perform, and reproducible method with a high level of sensitivity in detecting individuals with colorectal neoplasia. Combination of iFOBT and L-DNA improves the sensitivity for CRC and adenoma detection.