TY - JOUR
T1 - Clinical performance of an automated stool DNA assay for detection of colorectal neoplasia
AU - Lidgard, Graham P.
AU - Domanico, Michael J.
AU - Bruinsma, Janelle J.
AU - Light, James
AU - Gagrat, Zubin D.
AU - Oldham-Haltom, Rebecca L.
AU - Fourrier, Keith D.
AU - Allawi, Hatim
AU - Yab, Tracy C.
AU - Taylor, William R.
AU - Simonson, Julie A.
AU - Devens, Mary
AU - Heigh, Russell I.
AU - Ahlquist, David A.
AU - Berger, Barry M.
N1 - Funding Information:
Funding Funded by Exact Sciences Corporation (Madison, WI) and grants from Charles Oswald Foundation and Mayo Clinic .
PY - 2013/10
Y1 - 2013/10
N2 - 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 Pvalue). 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.
AB - 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 Pvalue). 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.
KW - BMP3
KW - Colon Cancer
KW - Early Detection
KW - NDRG4
KW - QuARTS
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UR - http://www.scopus.com/inward/citedby.url?scp=84884356620&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2013.04.023
DO - 10.1016/j.cgh.2013.04.023
M3 - Article
C2 - 23639600
AN - SCOPUS:84884356620
SN - 1542-3565
VL - 11
SP - 1313
EP - 1318
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 10
ER -