Stool methylated DNA markers decrease following colorectal cancer resection--implications for surveillance

Dig Dis Sci. 2014 Aug;59(8):1764-7. doi: 10.1007/s10620-014-3265-5. Epub 2014 Jul 4.

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Bone Morphogenetic Protein 3 / genetics*
  • Bone Morphogenetic Protein 3 / metabolism
  • Case-Control Studies
  • Colectomy
  • Colorectal Neoplasms / chemistry*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / surgery
  • DNA Methylation*
  • Feces / chemistry*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Population Surveillance

Substances

  • BMP3 protein, human
  • Biomarkers, Tumor
  • Bone Morphogenetic Protein 3
  • Muscle Proteins
  • NDRG4 protein, human
  • Nerve Tissue Proteins