Algorithm Development and Early Performance Evaluation of a Next-Generation Multitarget Stool DNA Screening Test for...

Area of Science:

• Oncology
• Gastroenterology
• Molecular Diagnostics

Background:

• The multitarget stool DNA (mt-sDNA) assay is a noninvasive screening method for average-risk colorectal cancer (CRC).
• A next-generation mt-sDNA test was developed using a new biomarker panel to enhance specificity while maintaining or increasing sensitivity.

Purpose of the Study:

• To establish an algorithm and cutoff for the next-generation mt-sDNA test.
• To validate the performance of this next-generation test using archived samples from the DeeP-C study.

Main Methods:

• Algorithm development involved 3011 samples, with cross-validation to ensure reliability.
• Validation utilized archived samples from the DeeP-C study, including 57 CRC cases, 583 advanced precancerous lesions (APLs), and 7022 negative samples.
• The next-generation test incorporated methylated DNA markers (CERKL4, LRRCC4, PPP2R2C, ZNFDC1) and fecal hemoglobin.

Main Results:

• The next-generation mt-sDNA test achieved 93.0% sensitivity for CRC and 48.4% sensitivity for APLs.
• Specificity was 88.5% for the absence of advanced neoplasia and 90.4% for non-neoplastic findings or negative colonoscopy.
• Algorithm development and cross-validation confirmed the reliability and reproducibility of the test.

Conclusions:

• The next-generation mt-sDNA test demonstrates promising performance for CRC screening based on archived samples.
• Further prospective validation in the BLUE-C study is planned to fully assess its clinical utility.