Table S2 from Next-generation Multi-target Stool DNA Panel Accurately Detects Colorectal Cancer and Advanced Precancerous Lesions

Gagrat, Zubin D.; Krockenberger, Martin; Bhattacharya, Abhik; Gagrat, Bridget Z.; Leduc, Christine M.; Matter, Michael B.; Fourrier, Keith D.; Mahoney, Douglas W.; Edwards V, David K.; Lidgard, Graham P.; Limburg, Paul J.; Johnson, Scott C.; Domanico, Michael J.; Kisiel, John B.

doi:10.1158/1940-6207.25338402.v1

capr-23-0285_table_s2_suppst2.docx (15.3 kB)

Table S2 from Next-generation Multi-target Stool DNA Panel Accurately Detects Colorectal Cancer and Advanced Precancerous Lesions

journal contribution

posted on 2024-03-04, 22:22 authored by Zubin D. Gagrat, Martin Krockenberger, Abhik Bhattacharya, Bridget Z. Gagrat, Christine M. Leduc, Michael B. Matter, Keith D. Fourrier, Douglas W. Mahoney, David K. Edwards V, Graham P. Lidgard, Paul J. Limburg, Scott C. Johnson, Michael J. Domanico, John B. Kisiel

Table S2: Subject demographics for the marker selection study for novel multi-target stool DNA panel.

History

ARTICLE ABSTRACT

The multi-target stool DNA (mt-sDNA) test screens for colorectal cancer by analyzing DNA methylation/mutation and hemoglobin markers to algorithmically derive a qualitative result. A new panel of highly discriminant candidate methylated DNA markers (MDM) was recently developed. Performance of the novel MDM panel, with hemoglobin, was evaluated in a simulated screening population using archived stool samples weighted to early-stage colorectal cancer and prospectively collected advanced precancerous lesions (APL). Marker selection study (MSS) and separate preliminary independent verification studies (VS) were conducted utilizing samples from multi-center, case–control studies. Sample processing included targeted MDM capture, bisulfite conversion, and MDM quantitation. Fecal hemoglobin was quantified using ELISA. Samples were stratified into 75%/25% training-testing sets; model outcomes were cross-validated 1,000 times. All laboratory operators were blinded. The MSS included 232 cases (120 colorectal cancer/112 APLs) and 490 controls. The VS featured 210 cases (112 colorectal cancer/98 APLs) and 567 controls; APLs were 86.7% adenomas and 13.3% sessile serrated lesions (SSL). Average age was 65.5 (cases) and 63.2 (controls) years. Mean sensitivity in the VS from cross-validation was 95.2% for colorectal cancer and 57.2% for APLs, with specificities of 89.8% (no CRC/APLs) and 92.4% (no neoplasia). Subgroup analyses showed colorectal cancer sensitivities of 93.4% (stage I) and 94.2% (stage II). APL sensitivity was 82.9% for high-grade dysplasia, 73.4% for villous lesions, 49.8% for tubular lesions, and 30.2% for SSLs. These data support high sensitivity and specificity for a next-generation mt-sDNA test panel. Further evaluation of assay performance will be characterized in a prospective, multi-center clinical validation study (NCT04144738). This study highlights performance of the next-generation mt-sDNA test, which exhibits high sensitivity and specificity for detecting colorectal cancer and APLs. This noninvasive option has potential to increase screening participation and clinical outcomes. A multi-center, clinical validation trial is underway.See related commentary by Bresalier, p. 93