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

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

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

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.

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.

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.