一种基于MassARRAY的简单且高度特异的粪便DNA检测方法，用于对粪便免疫化学检测呈阳性的个体进行后续决策的优先级排序。
A Simple and Highly Specific MassARRAY-Based Stool DNA Assay to Prioritize Follow-up Decisions in Fecal Immunochemical Test-Positive Individuals.
作者信息
Chang Pi-Yueh, Chen Chia-Chun, Chiang Jy-Ming, Chang Shih-Cheng, Wang Mei-Chia, Chen Jinn-Shiun, Tsai Wen-Sy, You Jeng Fu, Lu Jang-Jih
机构信息
Department of Laboratory Medicine, Chang Gung Memorial Hospital at LinKou Taoyuan 33305, Taiwan.
Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan 33302, Taiwan.
出版信息
Cancers (Basel). 2019 Mar 25;11(3):423. doi: 10.3390/cancers11030423.
BACKGROUND
Seventy-five percent of fecal immunochemical test (FIT)-positive individuals are false positives and undergo unnecessary colonoscopies. Here, we established a stool DNA (sDNA) test that uses the Single Allele Base Extension Reaction (SABER) MassARRAY platform to improve the accuracy of FIT-based CRC detection.
METHODS
Twenty-one variants in five CRC-associated genes were selected for the sDNA panel. Cell line DNA and matched mutation-confirmed tissue and stool samples from 34 patients were used for accuracy assessment (cohort 1). The clinical performance of the sDNA assay was further evaluated in 101 independent FIT-positive stool samples (cohort 2).
RESULTS
In cohort 1, we obtained a 62% mutation concordance rate in paired tissue and stool samples of the CRC group, regardless of the FIT status. In cohort 2, 100% specificity in normal controls with positive FIT results was observed. By weighting the FIT value and the presence of a given variant type in stool and then summing the two scores, we found that a one-increment increase in the score was associated with a 4.538-fold risk (95% CI = 2.121⁻9.309) for malignancy in the FIT-positive setting.
CONCLUSIONS
Our highly specific sDNA assay can help prioritize the most at-risk FIT-positive persons to receive prompt colonoscopic confirmation of CRC.
背景
粪便免疫化学检测（FIT）呈阳性的个体中有75%为假阳性，并接受了不必要的结肠镜检查。在此，我们建立了一种粪便DNA（sDNA）检测方法，该方法使用单等位基因碱基延伸反应（SABER）质谱分析平台来提高基于FIT的结直肠癌（CRC）检测的准确性。
方法
从五个与CRC相关的基因中选择21个变异体用于sDNA检测板。使用细胞系DNA以及来自34例患者的匹配的经突变确认的组织和粪便样本进行准确性评估（队列１）。在101份独立的FIT阳性粪便样本中进一步评估sDNA检测的临床性能（队列2）。
结果
在队列1中，无论FIT状态如何，我们在CRC组的配对组织和粪便样本中获得了62%的突变一致率。在队列2中，观察到FIT结果为阳性的正常对照的特异性为100%。通过对FIT值以及粪便中给定变异体类型的存在情况进行加权，然后将两个分数相加，我们发现分数每增加一个单位，在FIT阳性情况下发生恶性肿瘤的风险增加4.538倍（95%CI=2.121⁻9.309）。
结论
我们高度特异的sDNA检测方法有助于对风险最高的FIT阳性个体进行优先排序，以便及时通过结肠镜检查确诊CRC。
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