Hypermethylation of SFRP Genes in Stool DNA Test: A Future Technology in Colorectal Cancer Screening

Aims: Stool DNA test is considered as a future technology in screening for colorectal cancer (CRC). Both genetic and epigenetic changes in shed cells from gastrointestinal tumors into stool could be detected. Potentially, both premalignant adenomas and CRC may be detected this way. 90% of CRC seem to be sporadic and 10% hereditary. Age, diet, and environment have been suggested to induce epigenetic changes that may contribute to the development of sporadic CRC. Epigenetic hypermethylation can result in transcriptional silencing of tumor suppressor genes and is considered to be a key event of sporadic colorectal carcinogenesis. SFRPs (secreted frizzeld-related protein–1 and 2) are tumor suppressor proteins that contain a domain similar to one of WNT-receptor proteins and inhibit WNT-receptor binding to its signal transduction molecules. Detection of hypermethylation of SFRP1 and SFRP2 genes in human DNA isolated from stools might provide a novel strategy for the detection and investigation of sporadic CRC. Our study aims to prove the methylation status of SFRP genes in stool samples. Methods: To explore the feasibility of stool DNA test, fecal samples are obtained from 70 CRC patients. A further 30 fecal samples are obtained from patients without evidence of gastrointestinal neoplasia or disease. Isolated genomic DNA from stool is modified with sodium bisulfite and analyzed by specific PCR for methylation of SFRP1 and SFRP2 promoters. Results: With the stool DNA test we are able to detect hypermethylation in the promoterregions of SFRP1 and SFRP2 genes in the fecal DNA from colorectal cancer patients. Conclusion: The hypermethylation of SFRP1 and SFRP2 genes in the stool DNA test has a high sensitivity and specificity for sporadic CRC and may be valuable for screening purposes. Compared with current colorectal cancer screening methods, stool DNA test is more patient-friendly, non-invasive, more sensitive and specific. The cost-effectiveness of screening may also be improved. This new diagnostic tool may yield benefits in earlier detection and in the design of better antitumor interventions.

Keywords: Hypermethylation, Screening, Stool DNA