Diagnostic value of methylation status of T-UCRs for colorectal cancer

Background

Expression of Transcribed Ultra Conserved Regions (T-UCRs) is often dysregulated in various types of cancer. Regulation of T-UCR expression includes epigenetic mechanisms, and in particular CpG island methylation. Three T-UCRs (160, 283 and 346) have been found to be methylated in colon adenocarcinomas. The present study assesses the use of the T-UCR methylation status in circulating DNA as a diagnostic marker for colorectal cancer (CRC).

Methods

Expression and methylation levels of T-UCRs 160, 283 and 346 were assessed in neoplastic and paired normal colonic fresh frozen tissue specimens from 75 CRC patients, as well as in 5 fresh frozen adenoma tissue specimens. Methylation status of the three T-UCRs was also determined in plasma from 161 patients (56 CRC patients, 55 adenoma patients, 40 healthy subjects and 10 patients with colon inflammation or diverticulosis).

Results

Expression levels of all three T-UCRs were lower in neoplastic tissues, compared to normal adjacent colonic tissues, but only in T-UCR 160 the difference was statistically significant (p 

Conclusions

Methylation of T-UCR 160 in plasma has great specificity for CRC but low sensitivity. Alteration of the methodological approaches to improve the sensitivity could result in a promising non-invasive screening method for CRC.

Clinical trial identification

Legal entity responsible for the study

University of Patras

Funding

University of Patras

Disclosure

T. Makatsoris: Travel Pfizer, Roche, Astellas. Advisory: Roche, Boehringer. Honoraria: Roche, Sanofi, Merck, Amgen. H. Kalofonos: Travel: Pfizer, Roche, Novartis, Enorasis Advisory: Roche, Novartis, MSD, Genesis, Pfizer, Lilly, Leo, Amgen, Janssen, Merck, Merck Serono. Research Funding: Roche, Novartis, MSD, Genesis, Pfizer, Lilly, Bayer, Amgen, Janssen, Merck Serono. All other authors have declared no conflicts of interest.