Multitarget Stool mRNA Test for Detecting Colorectal Cancer Lesions Including Advanced Adenomas

SIMPLE SUMMARY: Colorectal cancer is still one of the deadliest cancers, even though its detection at early stages has been shown to be a key factor for reducing mortality. Screening methods are available, but their efficacy for detecting early-stage lesions is limited. In the present discovery stage study, we used a targeted mRNA assay in the stools to optimize the identification of patients bearing precancerous lesions as well as colorectal cancers at curable stages with only five targets, thus compatible with standard multiplex PCR. Although further validation is required, this assay has high potential for improving colorectal cancer screening efficacy. ABSTRACT: 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.