BACKGROUND & AIMS: Colorectal cancer (CRC) and advanced precancers can be detected noninvasively by analyses of exfoliated DNA markers and hemoglobin in stool. Practical and cost-effective application of a stool DNA-based (sDNA) test for general CRC screening requires high levels of accuracy and high-capacity throughput. We optimized an automated sDNA assay and evaluated its clinical performance. METHODS: In a blinded, multicenter, case-control study, we collected stools from 459 asymptomatic patients before screening or surveillance colonoscopies and from 544 referred patients. Cases included CRC (n = 93), advanced adenoma (AA) (n = 84), or sessile serrated adenoma ≥1 cm (SSA) (n = 30); controls included nonadvanced polyps (n = 155) or no colonic lesions (n = 641). Samples were analyzed by using an automated multi-target sDNA assay to measure β-actin (a marker of total human DNA), mutant KRAS, aberrantly methylated BMP3 and NDRG4, and fecal hemoglobin. Data were analyzed by a logistic algorithm to categorize patients as positive or negative for advanced colorectal neoplasia (CRC, advanced adenoma, and/or SSA ≥1 cm). RESULTS: At 90% specificity, sDNA analysis identified individuals with CRC with 98% sensitivity. Its sensitivity for stage I cancer was 95%, for stage II cancer it was 100%, for stage III cancer it was 96%, for stage IV cancer it was 100%, and for stages I-III cancers it was 97% (nonsignificant P value). Its sensitivity for advanced precancers (AA and SSA) ≥1 cm was 57%, for >2 cm it was 73%, and for >3 cm it was 83%. The assay detected AA with high-grade dysplasia with 83% sensitivity. CONCLUSIONS: We developed an automated, multi-target sDNA assay that detects CRC and premalignant lesions with levels of accuracy previously demonstrated with a manual process. This automated high-throughput system could be a widely accessible noninvasive approach to general CRC screening.
BACKGROUND & AIMS:Colorectal cancer (CRC) and advanced precancers can be detected noninvasively by analyses of exfoliated DNA markers and hemoglobin in stool. Practical and cost-effective application of a stool DNA-based (sDNA) test for general CRC screening requires high levels of accuracy and high-capacity throughput. We optimized an automated sDNA assay and evaluated its clinical performance. METHODS: In a blinded, multicenter, case-control study, we collected stools from 459 asymptomatic patients before screening or surveillance colonoscopies and from 544 referred patients. Cases included CRC (n = 93), advanced adenoma (AA) (n = 84), or sessile serrated adenoma ≥1 cm (SSA) (n = 30); controls included nonadvanced polyps (n = 155) or no colonic lesions (n = 641). Samples were analyzed by using an automated multi-target sDNA assay to measure β-actin (a marker of total human DNA), mutant KRAS, aberrantly methylated BMP3 and NDRG4, and fecal hemoglobin. Data were analyzed by a logistic algorithm to categorize patients as positive or negative for advanced colorectal neoplasia (CRC, advanced adenoma, and/or SSA ≥1 cm). RESULTS: At 90% specificity, sDNA analysis identified individuals with CRC with 98% sensitivity. Its sensitivity for stage I cancer was 95%, for stage II cancer it was 100%, for stage III cancer it was 96%, for stage IV cancer it was 100%, and for stages I-III cancers it was 97% (nonsignificant P value). Its sensitivity for advanced precancers (AA and SSA) ≥1 cm was 57%, for >2 cm it was 73%, and for >3 cm it was 83%. The assay detected AA with high-grade dysplasia with 83% sensitivity. CONCLUSIONS: We developed an automated, multi-target sDNA assay that detects CRC and premalignant lesions with levels of accuracy previously demonstrated with a manual process. This automated high-throughput system could be a widely accessible noninvasive approach to general CRC screening.
Authors: Erica K Barnell; Yiming Kang; Andrew R Barnell; Kimberly R Kruse; Jared Fiske; Zachary R Pittz; Adnan R Khan; Thomas A Huebner; Faith L Holmes; Malachi Griffith; Obi L Griffith; Aadel A Chaudhuri; Elizabeth M Wurtzler Journal: Clin Transl Gastroenterol Date: 2021-05-24 Impact factor: 4.488
Authors: Theodore R Levin; Douglas A Corley; Christopher D Jensen; Amy R Marks; Wei K Zhao; Alexis M Zebrowski; Virginia P Quinn; Lawrence W Browne; William R Taylor; David A Ahlquist; Graham P Lidgard; Barry M Berger Journal: Dig Dis Sci Date: 2017-01-02 Impact factor: 3.199
Authors: Bradley W Anderson; Yun-Suhk Suh; Boram Choi; Hyuk-Joon Lee; Tracy C Yab; William R Taylor; Brian A Dukek; Calise K Berger; Xiaoming Cao; Patrick H Foote; Mary E Devens; Lisa A Boardman; John B Kisiel; Douglas W Mahoney; Seth W Slettedahl; Hatim T Allawi; Graham P Lidgard; Thomas C Smyrk; Han-Kwang Yang; David A Ahlquist Journal: Clin Cancer Res Date: 2018-05-29 Impact factor: 12.531
Authors: Chung Wah Wu; Xiaoming Cao; Calise K Berger; Patrick H Foote; Douglas W Mahoney; Julie A Simonson; Bradley W Anderson; Tracy C Yab; William R Taylor; Lisa A Boardman; John B Kisiel; David A Ahlquist Journal: Dig Dis Sci Date: 2017-06-28 Impact factor: 3.199
Authors: Benjamin B Strauss; Tracy C Yab; Helen M O'Connor; William R Taylor; Douglas W Mahoney; Julie A Simonson; John Christensen; Suresh T Chari; David A Ahlquist Journal: Dig Dis Sci Date: 2015-08-22 Impact factor: 3.199
Authors: Dennis Yang; Shauna L Hillman; Ann M Harris; Pamela S Sinicrope; Mary E Devens; David A Ahlquist Journal: World J Gastroenterol Date: 2014-05-07 Impact factor: 5.742