The Stool DNA Test Is More Accurate Than the Plasma Septin 9 Test in Detecting Colorectal Neoplasia

David A. Ahlquist, William R. Taylor, Douglas W. Mahoney, Hongzhi Zou, Michael Domanico, Stephen N Thibodeau, Lisa Allyn Boardman, Barry M. Berger, Graham P. Lidgard

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Several noninvasive tests have been developed for colorectal cancer (CRC) screening. We compared the sensitivities of a multimarker test for stool DNA (sDNA) and a plasma test for methylated septin 9 (SEPT9) in identifying patients with large adenomas or CRC. Methods: We analyzed paired stool and plasma samples from 30 patients with CRC and 22 with large adenomas from Mayo Clinic archives. Stool (n = 46) and plasma (n = 49) samples from age- and sex-matched patients with normal colonoscopy results were used as controls. The sDNA test is an assay for methylated BMP3, NDRG4, vimentin, and TFPI2; mutant KRAS; the β-actin gene, and quantity of hemoglobin (by the porphyrin method). It was performed blindly at Exact Sciences (Madison, Wisconsin); the test for SEPT9 was performed at ARUP Laboratories (Salt Lake City, Utah). Results were considered positive based on the manufacturer's specificity cutoff values of 90% and 89%, respectively. Results: The sDNA test detected adenomas (median, 2 cm; range, 1-5 cm) with 82% sensitivity (95% confidence interval [CI], 60%-95%); SEPT9 had 14% sensitivity (95% CI, 3%-35%; P = .0001). The sDNA test identified patients with CRC with 87% sensitivity (95% CI, 69%-96%); SEPT9 had 60% sensitivity (95% CI, 41%-77%; P = .046). The sDNA test identified patients with stage I-III CRC with 91% sensitivity (95% CI, 71%-99%); SEPT9 had 50% sensitivity (95% CI, 28%-72%; P = .013); for stage IV CRC, sensitivity values were 75% (95% CI, 35%-97%) and 88% (95% CI, 47%-100%), respectively (P = .56). False positive rates were 7% for the sDNA test and 27% for SEPT9. Conclusions: Based on analyses of paired samples, the sDNA test detects nonmetastatic CRC and large adenomas with significantly greater levels of sensitivity than the SEPT9 test. These findings might be used to modify approaches for CRC prevention and early detection.

Original languageEnglish (US)
JournalClinical Gastroenterology and Hepatology
Volume10
Issue number3
DOIs
StatePublished - Mar 2012

Fingerprint

Septins
Colorectal Neoplasms
Confidence Intervals
DNA
Adenoma
Neoplasms
Porphyrins
Vimentin
Colonoscopy
Early Detection of Cancer
Actins
Hemoglobins

Keywords

  • Adenoma Detection
  • Colorectal Cancer
  • Plasma Septin 9
  • Stool DNA

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

The Stool DNA Test Is More Accurate Than the Plasma Septin 9 Test in Detecting Colorectal Neoplasia. / Ahlquist, David A.; Taylor, William R.; Mahoney, Douglas W.; Zou, Hongzhi; Domanico, Michael; Thibodeau, Stephen N; Boardman, Lisa Allyn; Berger, Barry M.; Lidgard, Graham P.

In: Clinical Gastroenterology and Hepatology, Vol. 10, No. 3, 03.2012.

Research output: Contribution to journalArticle

Ahlquist, David A. ; Taylor, William R. ; Mahoney, Douglas W. ; Zou, Hongzhi ; Domanico, Michael ; Thibodeau, Stephen N ; Boardman, Lisa Allyn ; Berger, Barry M. ; Lidgard, Graham P. / The Stool DNA Test Is More Accurate Than the Plasma Septin 9 Test in Detecting Colorectal Neoplasia. In: Clinical Gastroenterology and Hepatology. 2012 ; Vol. 10, No. 3.
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AU - Domanico, Michael

AU - Thibodeau, Stephen N

AU - Boardman, Lisa Allyn

AU - Berger, Barry M.

AU - Lidgard, Graham P.

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N2 - Background & Aims: Several noninvasive tests have been developed for colorectal cancer (CRC) screening. We compared the sensitivities of a multimarker test for stool DNA (sDNA) and a plasma test for methylated septin 9 (SEPT9) in identifying patients with large adenomas or CRC. Methods: We analyzed paired stool and plasma samples from 30 patients with CRC and 22 with large adenomas from Mayo Clinic archives. Stool (n = 46) and plasma (n = 49) samples from age- and sex-matched patients with normal colonoscopy results were used as controls. The sDNA test is an assay for methylated BMP3, NDRG4, vimentin, and TFPI2; mutant KRAS; the β-actin gene, and quantity of hemoglobin (by the porphyrin method). It was performed blindly at Exact Sciences (Madison, Wisconsin); the test for SEPT9 was performed at ARUP Laboratories (Salt Lake City, Utah). Results were considered positive based on the manufacturer's specificity cutoff values of 90% and 89%, respectively. Results: The sDNA test detected adenomas (median, 2 cm; range, 1-5 cm) with 82% sensitivity (95% confidence interval [CI], 60%-95%); SEPT9 had 14% sensitivity (95% CI, 3%-35%; P = .0001). The sDNA test identified patients with CRC with 87% sensitivity (95% CI, 69%-96%); SEPT9 had 60% sensitivity (95% CI, 41%-77%; P = .046). The sDNA test identified patients with stage I-III CRC with 91% sensitivity (95% CI, 71%-99%); SEPT9 had 50% sensitivity (95% CI, 28%-72%; P = .013); for stage IV CRC, sensitivity values were 75% (95% CI, 35%-97%) and 88% (95% CI, 47%-100%), respectively (P = .56). False positive rates were 7% for the sDNA test and 27% for SEPT9. Conclusions: Based on analyses of paired samples, the sDNA test detects nonmetastatic CRC and large adenomas with significantly greater levels of sensitivity than the SEPT9 test. These findings might be used to modify approaches for CRC prevention and early detection.

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KW - Colorectal Cancer

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