Clinical performance of an automated stool DNA assay for detection of colorectal neoplasia

Graham P. Lidgard, Michael J. Domanico, Janelle J. Bruinsma, James Light, Zubin D. Gagrat, Rebecca L. Oldham-Haltom, Keith D. Fourrier, Hatim Allawi, Tracy C. Yab, William R. Taylor, Julie A. Simonson, Mary Devens, Russell I. Heigh, David A. Ahlquist, Barry M. Berger

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1313-1318
Number of pages6
JournalClinical Gastroenterology and Hepatology
Volume11
Issue number10
DOIs
StatePublished - Oct 2013

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Adenoma
Colorectal Neoplasms
DNA
Neoplasms
Early Detection of Cancer
Hemoglobins
Colonoscopy
Polyps
Genetic Markers
Case-Control Studies
Actins
Costs and Cost Analysis

Keywords

  • BMP3
  • Colon Cancer
  • Early Detection
  • NDRG4
  • QuARTS

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Lidgard, G. P., Domanico, M. J., Bruinsma, J. J., Light, J., Gagrat, Z. D., Oldham-Haltom, R. L., ... Berger, B. M. (2013). Clinical performance of an automated stool DNA assay for detection of colorectal neoplasia. Clinical Gastroenterology and Hepatology, 11(10), 1313-1318. https://doi.org/10.1016/j.cgh.2013.04.023

Clinical performance of an automated stool DNA assay for detection of colorectal neoplasia. / Lidgard, Graham P.; Domanico, Michael J.; Bruinsma, Janelle J.; Light, James; Gagrat, Zubin D.; Oldham-Haltom, Rebecca L.; Fourrier, Keith D.; Allawi, Hatim; Yab, Tracy C.; Taylor, William R.; Simonson, Julie A.; Devens, Mary; Heigh, Russell I.; Ahlquist, David A.; Berger, Barry M.

In: Clinical Gastroenterology and Hepatology, Vol. 11, No. 10, 10.2013, p. 1313-1318.

Research output: Contribution to journalArticle

Lidgard, GP, Domanico, MJ, Bruinsma, JJ, Light, J, Gagrat, ZD, Oldham-Haltom, RL, Fourrier, KD, Allawi, H, Yab, TC, Taylor, WR, Simonson, JA, Devens, M, Heigh, RI, Ahlquist, DA & Berger, BM 2013, 'Clinical performance of an automated stool DNA assay for detection of colorectal neoplasia', Clinical Gastroenterology and Hepatology, vol. 11, no. 10, pp. 1313-1318. https://doi.org/10.1016/j.cgh.2013.04.023
Lidgard, Graham P. ; Domanico, Michael J. ; Bruinsma, Janelle J. ; Light, James ; Gagrat, Zubin D. ; Oldham-Haltom, Rebecca L. ; Fourrier, Keith D. ; Allawi, Hatim ; Yab, Tracy C. ; Taylor, William R. ; Simonson, Julie A. ; Devens, Mary ; Heigh, Russell I. ; Ahlquist, David A. ; Berger, Barry M. / Clinical performance of an automated stool DNA assay for detection of colorectal neoplasia. In: Clinical Gastroenterology and Hepatology. 2013 ; Vol. 11, No. 10. pp. 1313-1318.
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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.

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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.

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