570P - Diagnostic value of methylation status of T-UCRs for colorectal cancer

Abstract

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). 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). 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 < 0.001). Methylation levels of 160, 283 and 346 were higher in colorectal cancer tissues compared to normal adjacent tissues (p < 0.001, p = 0.029 and p = 0.005 respectively). Notably, methylation levels of 160 and 346 in adenomas were higher than those in normal tissues but lower than those in cancer tissues. Methylation status of 160 in plasma differed significantly among the four different groups of patients (p = 0.024) and the difference increased when we compared methylation status in colorectal adenoma or adenocarcinoma patients with healthy subjects or patients with inflammation or diverticulosis (p = 0.007). When methylation status was used to predict if a subject has colorectal adenocarcinoma, specificity and sensitivity were 85% and 30% respectively. 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.