Telomere in colorectal cancer associated with distant metastases and predicted a poor prognosis.

Abstract

BackgroundTelomere is essential for chromosomal stability and its length has been proven to be related to prognosis in many malignant tumors. This study aims to investigate the relevance of telomere length with clinical and pathologic features and its prognostic value in colorectal cancer (CRC).MethodsTelomere status of CRC and adenoma cells were measured by telomere-specific quantitative fluorescent in situ hybridization (Q-FISH). The relative telomere length (RTL) was calculated as the mean telomere fluorescent intensity units (TFUs) in carcinoma cell divided by the TFU in cancer-associated fibroblast cell (CAF).ResultsOne hundred CRC patients, who were received surgery treatment during 2013 to 2014 and fifty-seven patients who underwent the examination of colonoscope and were confirmed as adenoma were enrolled. TFUs of carcinoma cell and CAF were statistically significantly lower than in adjacent mucosa cell (P=0.0079). Although there was no difference between the three kinds of adenoma cells (P=0.5457), TFU in adenoma cells was significantly lower than in CAF (P<0.0001) and independent with age. TFU and the RTL were statistically significantly lower in adenoma cells than in carcinoma (all P<0.0001). TFU of carcinoma cell in distant metastases patients were significantly lower than that without distant metastases patients (P=0.002). When cut by the median value of TFU of carcinoma cell and RTL, patients with a lower TFU or RTL had statistically significantly poorer overall survival (OS) (P=0.0027, HR: 4.6, 95% CI: 1.9–11.0; P=0.0163, HR: 2.95, 95% CI: 1.22–7.12) and disease-free survival (DFS) (P=0.0057, HR: 3.14, 95% CI: 1.40–7.06; P=0.0271, HR: 2.49, 95% CI: 1.11–5.59, respectively) than those patients with higher TFU or RTL. On multivariate analysis, the TFU of carcinoma cell was proved to be an independent prognostic value both for OS and DFS (P=0.0005, HR: 4.975, 95% CI: 1.616–15.385; P=0.007, HR: 3.57, 95% CI: 1.410–9.010).ConclusionsThe length of telomere in carcinoma and adenoma cells were consistently shorter and the telomere changes were early carcinogenesis event, even the epithelial cells were morphologically not malignant. The length of telomere was associated with tumor metastases and prognosis, suggesting telomere probably was an important cue of the biological behavior of CRC.