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Stool Methylated DNA Markers Decrease Following Colorectal Cancer Resection—Implications for Surveillance

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Abstract

Background

Molecular changes associated with colorectal cancer (CRC) are detected by stool deoxyribonucleic acid testing but could persist following tumor resection.

Aims

We sought to determine whether methylated gene markers in stool normalize after CRC resection.

Methods

We studied stools from 22 CRC cases before and after subtotal resection and from 80 colonoscopy-normal controls. In blinded fashion, target genes (methylated NDRG4 and BMP3) were captured from stool supernatant, bisulfite-treated, and assayed by quantitative allele-specific real-time target and signal amplification. Results were dichotomized at 95 % specificity cutoffs.

Results

Among CRC cases, median methylated NDRG4 and BMP3 levels decreased dramatically (4- to 15-fold) following resection, p = 0.003 and p < 0.0001, respectively. Among the 14 cases with elevated preoperative levels, 13 (93 %) fell into the normal range after surgery, p = 0.0002. A case whose stool methylated NDRG4 level increased sharply after surgery was found to have recurrent CRC.

Conclusions

Methylated gene marker levels clear from stool following CRC resection unless disease is present. Postoperative stool marker levels are informative and may be of value in surveillance.

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Fig. 1

Abbreviations

AJCC:

American Joint Committee on Cancer

CRC:

Colorectal cancer

DNA:

Deoxyribonucleic acid

Ln:

Natural logarithm

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Acknowledgments

This work was supported by NIH Grant Number K12 CA90628, the Charles Oswald Foundation, the Maxine and Jack Zarrow Family Foundation of Tulsa Oklahoma and the Carol M. Gatton Foundation for Digestive Diseases Research. QuARTS assay materials and some reagents were kindly supplied by Exact Sciences Corporation (Madison WI) at no cost.

Conflict of interest

Mayo Clinic has entered into an intellectual property development agreement with Exact Sciences (Madison, WI) whereby inventors (Ms. Yab, Mr. Taylor, Mr. Mahoney, Drs. Kisiel, and Ahlquist) could share in equity or future royalties in accordance with Mayo Clinic policy.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN, 55905, USA

    John B. Kisiel, Tracy C. Yab, William R. Taylor & David A. Ahlquist

  2. Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA

    Douglas W. Mahoney

Authors
  1. John B. Kisiel
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  2. Tracy C. Yab
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  3. William R. Taylor
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  4. Douglas W. Mahoney
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  5. David A. Ahlquist
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Correspondence to John B. Kisiel.

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Kisiel, J.B., Yab, T.C., Taylor, W.R. et al. Stool Methylated DNA Markers Decrease Following Colorectal Cancer Resection—Implications for Surveillance. Dig Dis Sci 59, 1764–1767 (2014). https://doi.org/10.1007/s10620-014-3265-5

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  • DOI: https://doi.org/10.1007/s10620-014-3265-5

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