New fecal bacterial signature for colorectal cancer screening reduces the fecal immunochemical test false-positive rate in a screening population.

Guidelines recommend routine screening for colorectal cancer (CRC) in asymptomatic adults starting at age 50. The most extensively used noninvasive test for CRC screening is the fecal immunochemical test (FIT), which has an overall sensitivity for CRC of approximately 61.0%-91.0%, which drops to 27.0%-67.0% for advanced adenomas. These figures contain a high false-positive rate and a low positive predictive value. This work aimed to develop a new, noninvasive CRC screening tool based on fecal bacterial markers capable of decreasing FIT false-positive rates in a FIT-positive population. We defined a fecal bacterial signature (RAID-CRC Screen) in a proof-of-concept with 172 FIT-positive individuals and validated the obtained results on an external cohort of 327 FIT-positive subjects. All study participants had joined the national CRC screening program. In the clinical validation of RAID-CRC Screen, a sensitivity of 83.9% and a specificity of 16.3% were obtained for the detection of advanced neoplasm lesions (advanced adenomas and/or CRC). FIT 20 μg/g produced 184 false-positive results. Using RAID-CRC Screen, this value was reduced to 154, thus reducing the false-positive rate by 16.3%. The RAID-CRC Screen test could be implemented in CRC screening programs to allow a significant reduction in the number of colonoscopies performed unnecessarily for FIT-positive participants of CRC screening programs.

Déclaration de conflit d'intérêts

I have read the journal's policy and the authors of this manuscript have the following competing interests: JGG, XA, MSP, MS, SRP, JA, LO, and MM are employees from GoodGut, a company who has received private and public funding. JGG, XA, MSP, MS, SRP, JA, LO and MM report grants from MINECO and from CDTI, during the conduct of the study. JGG, XA, MSP, and JG are also GoodGut shareholders, outside the submitted work. MSP, JGG, and XA are authors of the patent "METHOD FOR DIAGNOSING COLORECTAL CANCER FROM A HUMAN FECES SAMPLE BY QUANTITIVE PCR, PRIMERS AND KIT" with reference number PCT/EP2015/054451; MSP, JGG, XA, SRP and MMR are authors of the patent "IMPROVED METHOD FOR THE SCREENING DIAGNOSIS AND/OR MONITORING OF COLORECTAL ADVANCED NEOPLASIA, ADVANCED ADENOMA AND/OR COLORECTAL CANCER" with reference number 193821865-1118. The rest of the authors have nothing to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials.