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Cited by 119Pancreatic and Hepatic Oncology ResearchCancer Genomics and DiagnosticsEpigenetics and DNA Methylation

Stool DNA testing for the detection of pancreatic cancer: Assessment of methylation marker candidates

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Kisiel, John B., Yab, Tracy C., Taylor, William R., Chari, Suresh T., Petersen, Gloria M., Mahoney, Douglas W., Ahlquist, David A.·2012·Cancer
DOI 10.1002/cncr.26558PMC PMC3292683
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Abstract

BACKGROUND: Pancreatic cancer (PanC) presents at late stage with high mortality. Effective early detection methods are needed. Aberrantly methylated genes are unexplored as markers for noninvasive detection by stool testing. The authors aimed to select discriminant methylated genes and to assess accuracy of these and mutant KRAS in stool to detect PanC. METHODS: Nine target genes were assayed by real‐time methylation‐specific polymerase chain reaction (MSP) in bisulfite‐treated DNA from microdissected frozen specimens of 24 PanC cases and 30 normal colon controls. Archived stools from 58 PanC cases and 65 controls matched on sex, age, and smoking were analyzed. Target genes from fecal supernatants were enriched by hybrid capture, bisulfite‐treated, and assayed by MSP. KRAS mutations were assayed using the QuARTS technique. RESULTS: Areas under the receiver operating characteristics curves (AUCs) for tissue BMP3, NDRG4, EYA4, UCHL1, MDFI, Vimentin, CNTNAP2, SFRP2, and TFPI2 were 0.90, 0.79, 0.78, 0.78, 0.77, 0.77, 0.69, 0.67, and 0.66, respectively. The top 4 markers and mutant KRAS were evaluated in stool. BMP3 was the most discriminant methylation marker in stool. At 90% specificity, methylated BMP3 alone detected 51% of PanCs, mutant KRAS detected 50%, and combination detected 67%. AUCs for methylated BMP3, mutant KRAS, and combination in stool were 0.73, 0.75, and 0.85, respectively. CONCLUSIONS: This study demonstrates that stool assay of a methylated gene marker can detect PanC. Among candidate methylated markers discriminant in tissue, BMP3 alone performed well in stool. Combining methylated BMP3 and mutant KRAS increased stool detection over either marker alone. Cancer 2011;. © 2011 American Cancer Society.

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  • Blood remains the most commonly studied biospecimen for early detection, but many analytes are also present in other proximate samples, including pancreatic juice, stool, urine, saliva, and pancreatic cyst fluid.

    “In passing, it also needs to be stated that, although blood remains the most commonly studied biospecimen for early detection, many of the analytes are also present in other proximate samples, including pancreatic juice,53,54 stool,55 urine,56,57 saliva,58 and pancreatic cyst fluid.59”

    From Artificial Intelligence and Early Detection of Pancreatic Cancer: 2020 Summative Review (2021) · cites this paper as [55]

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Authors
Kisiel, J. B., Yab, T. C., Taylor, W. R., Chari, S. T., Petersen, G. M., Mahoney, D. W., & Ahlquist, D. A.
Affiliations
Mayo Clinic (US)
Corresponding author
Ahlquist, David A.
ORCID
Venue
Cancer
Publisher
Wiley
Published
2011-09-22
Volume
118
Issue
10
Pages
2623-2631
ISSN
  • 0008-543X (ISSN-L)
  • 1097-0142
DOI
10.1002/cncr.26558
PMC
PMC3292683
OpenAlex
W1981407851
Cited by
119
References
0
Citations by year
2026: 3 · 2025: 5 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 7 · 2020: 12 · 2019: 9 · 2018: 9 · 2017: 11 · 2016: 10 · 2015: 18 · 2014: 5 · 2013: 12 · 2012: 7
FWCI
3.78
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (P50CA102701)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK084567)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
pancreatic cancer, stool DNA testing, DNA methylation, BMP3, KRAS mutation, non-invasive cancer detection, early cancer detection, methylation biomarkers, fecal DNA, cancer screening
MeSH terms
DNA, Feces, Female, Humans, Male, Mutation, Pancreatic Neoplasms, Proto-Oncogene Proteins, Biomarkers, Case-Control Studies, Proto-Oncogene Proteins p21(ras), CA-19-9 Antigen, ras Proteins, DNA Methylation, Area Under Curve, Bone Morphogenetic Protein 3

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