Prognostic impact of telomeric repeat-containing RNA expression on long-term oncologic outcomes in colorectal cancer

Abstract

Telomeres are transcribed into long, noncoding telomeric repeat-containing RNAs (TERRA) that have been implicated in the regulation of telomerase, the enzyme that lengthens telomeres, in heterochromatin formation at telomeres, and in telomere stability. This study aimed to evaluate the correlation between TERRA expression and long-term oncologic outcomes in colorectal cancer (CRC). We evaluated 18p TERRA expression and telomere length using quantitative real-time PCR in 60 patients who underwent surgical resection for CRC between June 2008 and November 2010. Patients were grouped according to 18p TERRA expression, with 29 (48.3%) and 31 (51.7%) patients in the low and high TERRA expression groups, respectively. The median follow-up period was 80 months (range 2–103). The 18p TERRA expression was marginally significantly associated with preoperative carcinoembryonic antigen (CEA; P=.082) and was significantly associated with telomere length (P<.05). Multivariate analysis revealed that preoperative CEA (hazard ratio [HR], 2.728; 95% confidence interval [CI], 0.832–8.944, P=.098) and 18p TERRA expression (HR, 0.113; 95% CI, 0.011–1.126, P=.071) were marginally significant independent prognostic factors for overall survival (OS), whereas preoperative CEA (HR, 4.254; 95% CI, 1.394–12.985, P=.011) and 18p TERRA expression (HR, 0.108; 95% CI, 0.011–1.037, P=.054) were significant independent prognostic factors for disease-free survival (DFS). According to our prognostic model with 2 prognostic factors, the OS and DFS rate increased to 76.2% and 80.63%, respectively, in patients with high 18p TERRA expression and CEA levels 5 (P=.178, P=.057, respectively). 18p TERRA expression was marginally significantly associated with preoperative CEA and significantly associated with telomere length, rendering it a potential prognostic factor for long-term oncologic outcomes in CRC.