Herring Elizabeth, Tremblay Éric, McFadden Nathalie, Kanaoka Shigeru, Beaulieu Jean-François
Laboratory of Intestinal Physiopathology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Centre de Recherche du Centre Hospitalier, Universitaire de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Cancers (Basel). 2021 Mar 11;13(6):1228. doi: 10.3390/cancers13061228.
Current approved non-invasive screening methods for colorectal cancer (CRC) include FIT and DNA-FIT testing, but their efficacy for detecting precancerous lesions that are susceptible to progressing to CRC such as advanced adenomas (AA) remains limited, thus requiring further options to improve the detection of CRC lesions at earlier stages. One of these is host mRNA stool testing. The aims of the present study were to identify specific stool mRNA targets that can predict AA and to investigate their stability under a clinical-like setting. A panel of mRNA targets was tested on stool samples obtained from 102 patients including 78 CRC stage I-III and 24 AA as well as 32 healthy controls. Area under the receiver operating characteristic (ROC) curves were calculated to establish sensitivities and specificities for individual and combined targets. Stability experiments were performed on freshly obtained specimens. Six of the tested targets were found to be specifically increased in the stools of patients with CRC and three in the stools of both AA and CRC patients. After optimization for the choice of the 5 best markers for AA and CRC, ROC curve analysis revealed overall sensitivities of 75% and 89% for AA and CRC, respectively, for a ≥95% specificity, and up to 75% and 95% for AA and CRC, respectively, when combined with the FIT score. Targets were found to be stable in the stools up to 3 days at room temperature. In conclusion, these studies show that the detection of host mRNA in the stools is a valid approach for the screening of colorectal cancerous lesions at all stages and is applicable to a clinical-like setup.
目前批准的用于结直肠癌（CRC）的非侵入性筛查方法包括粪便免疫化学检测（FIT）和DNA-FIT检测，但它们在检测易进展为CRC的癌前病变（如高级别腺瘤，AA）方面的功效仍然有限，因此需要更多选择来改善CRC病变的早期检测。其中一种方法是宿主mRNA粪便检测。本研究的目的是确定能够预测AA的特定粪便mRNA靶点，并研究它们在类似临床环境下的稳定性。对从102名患者获得的粪便样本进行了一组mRNA靶点检测，这些患者包括78例I-III期CRC患者、24例AA患者以及32名健康对照。计算受试者工作特征（ROC）曲线下面积，以确定单个和组合靶点的敏感性和特异性。对新鲜获取的标本进行稳定性实验。发现6个检测靶点在CRC患者的粪便中特异性升高，3个在AA和CRC患者的粪便中均升高。在优化选择AA和CRC的5个最佳标志物后，ROC曲线分析显示，对于AA和CRC，当特异性≥95%时，总体敏感性分别为75%和89%，与FIT评分相结合时，AA和CRC的敏感性分别高达75%和95%。发现靶点在室温下的粪便中可稳定存在3天。总之，这些研究表明，检测粪便中的宿主mRNA是筛查各阶段结直肠癌病变的有效方法，并且适用于类似临床的环境。
